ingestão de bicarbonato aumenta excreção eletrolítica

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88:540-550, 2000.J Appl PhysiolDonald G. Welsh and George J. F. HeigenhauserMichael I. Lindinger, Thomas W. Franklin, Larry C. Lands, Preben K. Pedersen,electrolyte excretion in humans

ingestion rapidly increases renal3and KHCO3NaHCO

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NaHCO3 and KHCO3 ingestion rapidly increases

renal electrolyte excretion in humans

MICHAEL I. LINDINGER,1 THOMAS W. FRANKLIN,1 LARRY C. LANDS,2

PREBEN K. PE DERSEN,3 DONALD G. WELSH,1 AND GEORGE J. F. HEIGENHAUSER2

1Dep ar tm en t of H u m an B iol ogy an d N u tr it ion al S cien ces, Un iv ers it y of Gu elp h , Gu elp h N 1G 2W 1;2Dep ar tm en t of M ed icin e, M cM as ter U n iv ers it y, H am il ton , On ta ri o, Ca n ad a L 8N 3Z 5; an d3Dep ar tm en t of S por ts S cien ce an d Ph ys ica l E d u cat ion , U n iv ersit y of Od en se,

DK 52 30 Od en se, Den m ar k

Li ndi nge r, M i c hae l I ., Thom a s W. F r ank l i n, Lar r y C.

L a n d s, P r e b e n K. P e d e r s e n , D o n a l d G . We l s h , a n dG e or ge J . F. H e i ge nha us e r . Na HCO3 and KHCO3 ingestionrapidly increases renal electrolyte excretion in humans. J .

App l. Ph ysiol . 88: 540550, 2000.This paper describes andqua nt ifies acute responses oft he kidneys in corr ecting plasmavol ume , a ci d-ba se , a n d i on di st urba nc es re sul t i ng from

Na HCO3 a nd KHCO3 ingestion. Renal excretion of ions andwater was st udied in five men after ingestion of 3.57 mmol/kgbody m ass of sodium bicarbonate (NaHCO3) a nd, i n a se pa -rate trial, potassium bicarbonate (KHCO3). Subjects had aFole y c a t he t er i nsert e d i nt o t he bla dde r a nd i ndwe ll ingca t he t e rs pla c ed i nt o a n a nt e cubi t a l vei n a nd a bra chi a lartery. Blood and urine were sampled in the 30-min periodbefore, the 60-min period dur ing, and the 210-min periodafter ingest ion of th e solut ions. Na HCO 3 ingestion resulted ina rapid, tran sient diuresis and na triur esis. Cumu lative urineoutput was 44 11% of ingested volume, resu lting in a 555 11 9 m l in cr ea s e i n t ot a l b od y w at er a t t h e e nd of t h eexperiment. The cumulative increase (above basal levels) inrenal Na excretion accounted for 24 2% of inges ted N a. I nt he KHCO3 t r i a l, a rt e ria l pl a sma K concentration rapidlyincreased from 4.25 0.10 to a pea k of 7.17 0.13 meq/l 140min a fter th e beginn ing of ingestion. This increa se result ed ina pronounc ed, t r a nsi ent di ure si s, wit h cumul a t i ve uri neoutput at 270 m in similar to the volume ingested, natriur esis,a nd a pronounce d ka l iure sis t h a t wa s ma i nt a i ne d unt i l t hee nd of t h e e xpe rime nt . Cumu l a t ive (a bove ba sa l ) re na l K

excretion at 270 min accounted for 26 5% of ingested K.The kidneys were importa nt in m ediating ra pid corrections ofsubstan tial portions of the fluid an d electrolyte distur bancesresu lting from ingestion of KHCO 3 a nd Na HCO3 solutions.

potassium bicarbonate; sodium bicarbonate; kidney; aldoste-rone; a cid-base; str ong ion difference; chloride; glomeru larfiltration r ate; ur ine alkalinization

IN ATTEMPTS TO IMPROVE short-term, h igh-intensity exer-cise per forman ce, Na HCO3 loading h as long been used(19). There is, however, little inform at ion r egar ding th etime course and magnitude of acute renal responses inhum ans who have ingested an amount of NaHCO3 t h a tmay be considered to be of ergogenic benefit (minimum

of 0.3 g/kg body mass). The chronic responses to in-gested or infused bicar bonat e solut ions in clinical situ a-tions have been extensively documented (2, 9, 14, 23,3 0, 3 7). Fe w s t u d ie s , h owev er , h a v e e xa m i n ed t h eeffects of ingested KHCO3 (37, 38), and there do notappear t o be studies that h ave compa red the ear ly rena lresponses to large, equimolar doses of NaHCO3 (suffi-cient to be of ergogenic benefit in h um ans, see Ref. 27)and KHCO3 in humans. The physicochemical origins ofplasma fluid and ion disturbances to ingested Na a n dK are expected to be different due to differences intheir distribution and cellular transport in the intes-tine, kidneys, mu scles, and other t issues (27). The bu lkof Na absorbed from the intestinal tract remains inthe extracellular fluids (ECFs) and, if not fully ex-creted, will result in an increased ECF volume (ECFV);on t he other han d, K rapidly enters intracellular fluidcompartments (27).

Although acute effects of KHCO3 ingestion have n otb ee n e xt e n s iv el y s t u d i ed i n h u m a n s (2 7, 3 7, 3 8), a

generalized comparison of the responses to NaHCO3a n d K H C O3 may be obtained from various studies.Ren a l r e s pon s e s t o i n ge s t ed or i n fu s e d Na HCO3 orNaCl and KHCO3 or KCl includ e increas ed excretion ofthe cation and water and a decreased reabsorption of H CO 3

(2, 30, 37). There are, however, some notabledifferences a mong r esponses, depen ding on th e cation(Na v s . K) a n d t h e a ccom p a n y in g a n i on (Cl orH CO 3

). NaH CO3 loading, compared with NaCl loading,results in increased renal excretion of K (U KV) (14)a n d N a (U NaV) (22), whereas NaCl loading has noeffect on U KV a n d C l

excretion (37). KCl loading,compared with NaCl loading, results in an increasedglomerular filtrat ion ra te (GFR) (29), increased plasma

aldosterone (30), and increased renal U KV a n d C l

excret ion (24, 30, 37, 38). KCl loading is a lso associat edwith decreases in plasma volume (PV) and ECFV (3, 37).KHCO3 loading, compared with KCl loading, results in aprolonged period of urine alkalinization associated withincreased HCO3

a n d Cl excretion and decreased ex-cretion of NH 4

(UNH 4V) an d t itr at able a cid (TA) (37).The main purposes of this paper are to describe and

interpret the acute renal contribution to the correctionof the volume, acid-base, and ion disturbances result-ing from NaHCO3 a n d KHCO3 loading in humans. Ana i m o f t h i s p a p e r i s t o i n t e gr a t e t h e r e n a l r e s p on s e s

The costs of publication of this a rticle were defrayed in pa rt by thep a ym e n t of p a g e ch a r g es . T h e a r t icle m u s t th e r e for e b e h e r e b ymar ked advertisement in accordan ce with 18 U.S.C. Section 1734solely to indicate th is fact.

J . A pp l. Ph ys iol.88: 540550, 2000.

8750-7587/00 $5.00 Copyright 2000 th e American Physiological Society540 h t t p://www.ja p.or g


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with the vascular and skeletal muscle responses de-scribed previously in these subjects (27). The hypoth-esis was tested that the kidneys play an important rolein the acute correction of fluid and ion disturbancesresulting from Na HCO3 a n d KHCO3 ingestion. It wasalso hypothesized tha t in the NaHCO 3 tria l, comparedwith the KHCO3 trial, the kidneys would excrete excesswater, solute, and base equivalents at a greater rate,

resulting in a m ore r apid correction of the fluid an d iondisturbance. This stu dy also ana lyzed u rine composi-tion with respect to the independent variables of acid-base contr ol in biological fluids, n amely t he str ong iondifference (SID) concent ra tion ([SID]), the tota l concen-tr ation of weak a cids an d bases ([Atot ]), an d th e concen-tr at ion of CO2 (28, 35). These th ree var iables determinethe measured concentrations of H a n d H C O3

([H]and [HCO3

], respectively), a nd an alysis of chan ges inthese variables provides insight as to the mechanismsof acid-base control.

METHODS

F i ve h e a lt h y m e n (a g e 2 9

2 yr , m a ss 8 0

5 k g )pa rt i ci pa t e d i n t hi s s t udy. Wri t t e n i nformed conse nt wa sobtained after the procedures and potential risks were fullyde sc ri be d t o t he subj e c t s. T he st udy wa s a pprove d by t heUniversitys hum an ethics committee. A sixth subject wastr eated for hyper kalemia (see Ref. 27); this individua ls dat awere excluded from the experiment.

E xp eri m en ta l pr otocol. In t he 24-h period before each trial,subjects abstained from caffeine and alcohol. About 2 h beforetheir arrival at the laboratory, the subjects ate a light meal(toasted brea d an d juice). All experiments began at 8:00 AMand consisted of1 h of pre pa ra t i on t i me a nd 5 h of da t acollection.

A bra chi a l a rt e ry a nd a nt e cubi t a l ve in (opposit e a rms)were catheterized percutan eously with a 20-gauge 1.25-in.-long Teflon cath eter (Angiocat h, Becton Dickinson, Baxt er,Mississauga, ON) after the skin was infiltrated with 0.5 ml of2% Xylocaine without epinephrine (Astra Pha rma , Missis-sa uga , ON). T he pa t e ncy of t he ca t he t e r wa s m a i nt a i nedusin g a slow saline drip (200 l/min). The ur inary t ract wasinfiltrated aseptically with Xylo-Gel (Astra Pharma) and aFoley urinary catheter (Baxter) inserted into the bladder. Theurina ry ana lgesic Pyridium (Parke-Davis, Scarborough, ON)was pr escribed for 1 3 days following each experiment .

After insertion of the catheters, each subject was seated ina comfort a bl e c ha i r for t he re ma i nder of t h e e xpe rime nt .During a 30-min baseline period, urine and blood sampleswere obtained at 15-min intervals. At th e end of this period(t i me 0), subjects ingested 3.57 mmol/kg body mass of eitherKHCO3 or NaHCO3 duri ng t he ne xt 60 mi n. T he 920 ml ofsolution ingested, which h ad an osmolar ity of600 m osmol/l,

was flavored with Kool-Aid and sweetened with Nutrasweet.T he orde r of pre se nt i ng t he e xpe ri me nt a l t re a t me nt s wa sra ndomi z e d for e a c h t ri a l , a nd t ri a l s we re se pa ra t e d by a tleast 2 wk to allow for n ormalization ofh emoglobin concentr a-tion. The subjects were observed for a further 210 min in thepostingestion period. Urine drain ed continu ously into a sealedcollection bag and was completely collected at 20-min inter-vals until 120 min and then at 30-min intervals until 270 min.

M eas u rem en ts an d an al ys is. Arterial an d venous bloodsa mpl ing a nd a na l ysi s ha ve be en de scri bed (27). Art e ria lp la s m a a l dos t e r on e con ce n t r a t ion w a s d e t er m i n ed b yRIA (Coat -A-Coun t TKAL1, Diagnostics P roducts, Los Ange-les, CA).

Urine volume was measured with graduated cylinders attimed int ervals for calculation of ur ine flow rate (UF R). Ur inepH was immediately measured (Brinkman Metrohm 632 pHmeter). Urine lactate and amm onium ([NH 4

]) concent ra tionswere measured by using enzymatic fluorometric techniques(5) on 400-l sam ples depr oteinized in 800 l of 6% perchloricacid. Urine P i concentration ([P i]) was a ssayed by spectropho-tometr ic an alysis (Sigma k it 670, Sigma Chem ical, St. Louis,

MO). Urine sodium ([Na

]), pota ssium ([K

]), and calcium([Ca 2]) conc ent ra t i ons were me a sure d, a ft e r a ppropri a t edilution in deionized water, using ion-selective electrodes(Nova Statprofile 5, Nova Biomedical, Waltham, MA). UrineCl concentr ation ([Cl]) was measured by coulometric titra-tion (Buchler-Cotlove chloridometer, Buchler Instr ument s,Fort Lee, NJ). Plasma and urine creatinine concentrationswere determined with the use of an enzymatic fluorometrictechnique (5) after u rine was fir st diluted 49:1 (20 l in 980 lH 2O) in deionized wa ter. Differences between du plicate mea-surements for the assays were 0.3 0.1 meq/l for [Na], 0.6 0.2 meq/l for Cl, 0.02 0.02 meq/l for [K], 0.2 0.2 meq/lfor [Ca 2] and 0.3 0.2 mmol/l for creatinine and phosphateconcentrations.

Urine TA minus bicarbonate concentration ([TAH CO 3])

was determined by using a double titra tion procedure (20) asdescribed previously (28). Briefly, immediately after collec-tion, a 15-ml sam ple of ur ine was acidified to below pH 5 with20 l of concentra ted (60%) nitric acid. The titr ation wasperformed on 1.0-ml urine sam ples by using pH a nd r eferen ceelectr odes (MI-406, MI-403, Microelectr odes, Londonder ry,NH) with a digital pH met er (PHM 73, Radiometer, Copenh a-gen, De nma rk). Humi dified room a i r (23.6 0.1C) wasbubbled through the urine samples for 15 min to complete theremoval of HCO3

from solution. A digital micrometer syringe(model S4200A, Roger Gilmont Instr ument s, Great Neck,NY) was used to dispense 0.1 N NaOH to titrate the sampleback to the corresponding arterial plasma pH.

Calculations. Urin e [TAH CO 3] was calculat ed after Hills

(20)

[TA H CO 3], m e q/l (EPBTV N b) (Va N a)

Vu(1)

where EPBTV is the end-point base titration volume (liters),or the volum e of base add ed to reach the desired pH en d point ;N b a n d N a a re t h e norma l it y of Na OH a nd HNO3; Vu i s t hevolume of urine tit ra ted (liters); an d Va is th e volum e of HNO 3added (liters) to remove the HCO3

. Net acid excretion wascalculat ed as U Na

4V TAH CO 3

excretion (UTAHCO3V).

Creatinine clearan ce was used a s an estimate of GFR andwas calculated as previously described (36). In normal sub-

ject s, du r in g t h e t im e of da y w h en t h e s t u dy wa s con du ct ed (8

AM to 1 PM), creatinine clearance reportedly exceeded GFRby a near ly constant 12 2 ml/min (mean SE , n 14; Ref.36). Therefore, the sma ll tubula r secretion of creatinin e is notexpected t o affect t he t ime cour se of the observed responses int he pre sent s t udy. Ion e xcre t i on ra t e s a nd i on fra c t iona lexcretions were calculated with standard equations (36).

Cumu lative electrolyte excretion was determined by inte-gration of ion excretion r ates over time. Basal electrolyteexcretion was calculated on t he basis of the preingestionexcretion rates. The difference between total cumulative andcumu lative basal excretion was referred to as extra andre pre se nt s t he a mount of i on e xcre t e d i n e xce ss of ba sa llevels.

54 1RENAL RESPONSES TO KHCO3 AND N AH CO 3 LOADING


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Urin e [SID] was calculated as t he sum of th e strong cationsminus t he sum of the str ong anions (35)

[SID] ([Na] [K] [Ca 2]) ([Cl] [lactate]) (2)

Urine [Atot ] a nd [HCO3] were calculated according to t he

following equation, which is consistent with the mass actionequilibria an d electr oneutr ality of solut ions (35)

[H

]4

(KA

[SID])

[H

]3

5([SID] [Atot ])(KA) (KC P CO2 Kw)6 [H]2

[(KC P CO2 Kw)(KA) (K3 Kc P CO2)] [H]

KA K3 KC P CO2 0

(3)

where at 37C the constants have the following values: KA 1.58 107 eq/l (the dissociation constant for the phosphatebuffer system; Ref. 18), KC 2.45 1011 (eq/l)2/mm H g (35 ),K3 6.0 10

11 eq/l (11) an d KW 4. 4 1014 (eq/l)2 (18).

Urine P CO2 was assum ed to equal art erial plasma P CO2 for th epurposes of these calculations (see Ref. 28).

The validity of the ph ysicochem ical met hod was verified bycalculating urine [Atot ] from me a sure d uri ne pH, [SID], aconsta nt P CO2 of 40 Torr, an d a KA for [Atot ] of 1.58 107 eq/l.Linear regression analysis of [Atot ] vs. [TAH CO 3

] yieldedt h e s ig nifi ca n t (P 0.0001; r2 0 .8 0 6) r e l a t ion[Atot ] 0.7950 0.0672 [TAH CO 3

]. This calculat ion alsoshowed that calculated urine [HCO3

] appr oximated [Atot ] a te a c h t i me poi nt i n bot h t ri a l s . Consi st e nt wi t h t he l a w of electr oneutr ality, the su m of [Atot ] and [HCO3

] equaled [SID]within 3.8 1.1%.

Statistics. Al l va lue s a re me a ns SE. Two-way ANOVAw it h r e p ea t e d m e a s u r e s w a s u s ed t o a n a l y ze d a t a w it hrespect to time an d tr eatment. When a significant Frat io wasobt a i ne d, t he St ude nt -Ne wma n-Ke ul s me t hod wa s use d t ocompa re me a ns. St a t i st ica l s ignifica nc e wa s a cce pt ed a tP 0.05.

RESULTS

Plasma acid-base state, ions, and aldosterone. I n t h eNa HCO3 trial, plasma [H] decreased by 7.8 3 neq/lby 60 min, compared with a 5.9 1.6 neq/l decrease int h e KHCO3 trial (Table 1). In both trials, plasma [H]remained significantly lower than initial levels untilt h e e n d of t h e e xp er im e n t . Wit h in 3 0 m in of t h e

b eg in n i n g of N a H C O 3 i n ge s t ion , a r t e r i a l p la s m a[HCO3

] increased and remained elevated until the endof the experiment . In th e KHCO3 trial, arter ial plasma [H CO 3

] increased above initial levels by 80 min andreturned toward initial values by 120 min. Detailedr e s pon s e s a n d i n t er p r e t a t ion for b ot h a r t e r i a l a n dvenous plasma have been published (27).

In the NaHCO3 trial, arterial plasma [Na] and [Cl]

did not chan ge (Table 1); in cont ra st, in th e KHCO 3 t r i a lboth [Na] a n d [Cl] significantly decreased between100 and 150 min, with [Na] rema ining depressed untilthe en d of the experiment . Plasma [K] and a ldosteroned i d n o t c h a n g e i n t h e Na HCO 3 trial (Fig. 1). In theKHCO3 trial, plasma [K] peaked at 7.17 0.13 meq/l

at 110 min and then slowly decreased to 5.1 0.8 by270 min. The increase in plasm a a ldosterone concentra -tion paralleled that of plasma [K], with aldosteroneconcentration exceeding 1 mol/l between 90 and 150min.

Water balance, GFR, an d UFR . I n t h e Na HCO3 trial,t h e r e w a s n o c h a n ge i n p la s m a v olu m e d u r in g t h eingestion period, a nd then plasma volume progres-sively increased, peaking at 7.5 2.0% above initiallevels at 210 min (Table 1). In contrast, in the KHCO3trial, ingestion of the solution resu lted in an immediateand pronoun ced decrease in plasma volume th at reached a

Table 1. Plasma ions and percent change in plasma volume before (time 0), during (20, 40, and 60 min),and after ingestion of NaHCO3 and KHCO3

Trial

Time, min

P r ein gest ion In gest ion P ost in gest ion

0 20 40 60 80 100 120 150 180 210 240 270

[Na ] NaHCO3 143.10.6

144.80.7

146.00.8

146.80.8

146.10.6

146.50.8

146.50.9

145.10.5

145.50.4

145.30.5

145.10.6

144.30.8

[Na ] KHCO3 143.20.2

142.80.3

142.40.3

142.30.2

141.50.3

140.9*0.6

140.9*0.4

141.3*0.3

141.1*0.2

140.9*0.3

141.4*0.3

141.5*0.5

[Cl] NaHCO3 106.30.3

105.90.4

104.50.8

104.30.9

102.90.9

103.70.9

102.41.3

104.10.9

103.50.8

104.40.6

103.41.3

103.01.1

[Cl] KHCO3 106.10.6

106.30.5

105.70.6

105.30.7

104.70.7

105.00.5

104.4*0.4

104.5*0.3

104.90.3

104.70.3

105.10.6

104.70.5

[HCO3

] NaHCO3 26.00.4 27.90.4 29.8*0.4 32.0*0.6 32.5*0.8 32.0*0.6 31.7*0.7 31.2*1.3 30.3*1.8 29.2*0.6 30.1*0.5 30.3*0.5

[HCO3] KHCO3 24.2

1.124.80.9

26.6*0.8

27.3*0.9

28.4*0.9

29.9*1.1

27.3*0.6

27.2*0.5

25.8*0.8

25.9*1.4

26.4*1.5

25.3*1.4

[H] NaHCO3 37.60.6

36.00.5

33.1*0.6

32.3*0.5

32.4*1.0

33.8*0.6

34.3*0.8

34.0*0.5

36.0*0.7

35.0*0.9

34.7*0.6

35.6*0.4

[H] KHCO3 39.30.9

38.50.6

38.00.7

35.7*1.8

35.5*0.7

34.1*1.8

34.7*1.0

36.0*0.7

36.4*0.8

36.0*0.6

35.4*1.3

37.3*0.5

%dPV NaHCO3 0.0 2.31.5

0.21.3

1.71.9

2.22.6

3.31.7

2.32.2

6.8*2.4

6.6*1.8

7.5*2.0

5.6*1.8

5.9*2.4

%dPV KHCO3 0.0 1.20.7

5.81.5

10.2*2.7

11.2*3.3

13.4*2.5

14.9*1.7

10.5*4.9

10.8*3.5

8.6*2.6

5.8*3.9

4.5*2.8

Values are means SE ; n 5. Ion concentr ations a re in meq/liter. %dPV, percent chan ge in plasma volume. Bra ckets denote concentra tion.*Significantly different from time 0, P 0.05; KHCO3 mean significant ly different from NaH CO3 m e a n , P 0.05.

54 2 RENAL RESPONSES TO KHCO3 AND N AH CO 3 LOADING


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nadir of14.9 1.7% below initial levels at 120 min;this was followed by a slow, significant partial recov-ery. Water balance summaries (Table 2) are based onestimat es of complete int estinal absorption of th e solu-tions by 270 min (see Ref. 27). The net increase in totalb o d y wa t e r i n t h e Na HCO3 t r i a l wa s 5 5 5 119 ml,compared with complete restoration of fluid balance(25 83 ml) in the KHCO 3 trial . In the NaHCO3 trial,the ECF compartment was in positive fluid balance,consistent with the retention of Na in the ECF com-partm ent (27). In contra st, in t he KHCO 3 trial , ECFVwas estimated to be in n egative balance by about 800

ml, consistent with a net movement of water into cells(27).

In the NaHCO3 trial, initial GFR was 90 18 ml/minand did not change throughout the experiment (Fig.2A ). I n con t r a s t , i n t h e KHCO3 trial , GFR increasedrapidly from 71 1 6 m l /m i n (t i m e 0) t o 3 0 6 45ml/min by 60 min an d rema ined elevated un til 120 min.

In the NaHCO3 trial, UFR increased two- to threefold

from 0.6 0.2 ml/min (t im e 0) t o 2 .6 0.4 ml/minb et w ee n 8 0 a n d 1 20 m in (F ig . 2B ). After KHCO3ingestion, UFR increased up to eightfold greater thaninitial within 80 min an d rema ined significant ly great erthan in the NaHCO3 trial un til 150 min.

S o d i u m . I n t h e Na HCO3 trial , 270 min after inges-tion of 280 meq of Na was begun, 10% of ingested Na

remained in the plasma compartment, 46% remainedin the interstit ial fluid compartm ent, and renal U NaVaccoun ted for 30% of ingested Na (Tab le 3).

I n t h e Na HCO3 trial , urine [Na] increased twofold

between the end of ingestion (123 2 7 m e q / l a t 6 0min) and 270 min (255 14 meq/l). U NaV was three-t o fou r fol d g r ea t e r t h a n in i t ia l v a lu e s b et w ee n80 and 180 min, and it remained elevated (298 14 e q/m i n ) a t 2 70 m i n com p a r e d wit h i n it i a l l ev el s

F ig. 1 . P la s m a K concentration ([K], solid symbols) and aldoste-rone concentr at ion ([aldoste rone], open sym bols) before (up t o 0 min),during (160 min), and after (61270 min) ingestion of NaHCO 3(squares) or KHCO3 (circles) at a dose of 3.57 m mol/kg body ma ss.Hatched bar indicates 60-min period of HCO 3 ingestion. Values ar em e a n s SE ; n 5. *[K] and a ldosterone concentr at ion significantlyincreased (P 0.05) compared with preingestion (20 and 0 min).[K] a nd [aldosterone] significantly greater in KHCO3 tr ial com-pared with NaHCO3 tr ial.

Table 2. Water balance with N aHCO 3 and KHCO3ingestion at 120 and 270 m in

Na HC O3 KHCO3

120 m in 270 m in 120 m in 270 m in

Fluid ingested,m l 93670 93670 91559 91559

Saline infused,m l 25136 43479 26029 43866

Blood sampling,m l 240 400 240 400

Urine volume,m l 20720 41536 50945* 92850*

P V, m l 69

57 173

67

45 3

79*

144

86*

ISF V, m l 311255 78030 3 2,039357* 650389*E CF V, m l 380311 95437 0 2,493436* 794475TBW, m l 74093 555119 42678* 2583*

Va lu e s a r e m e a n s SE ; n 5. Fluid ingested, fluid volumeaccompan ying the NaHCO 3 or KHCO3 dose; saline infused, measu redfrom iv drip at 270 min; blood sampling, estimated blood volume lossdue to blood sampling; ur ine volume, cumulative urine volumeproduced. PV, chan ge in art erial plasma volume; ISFV, change ininterstitial fluid volume; ECFV, change in extracellular fluid vol-ume; TBW, change in total body water. The change in ECFV wasp a r t i t ion e d b etw e en th e c ha n g es in P V a n d I S F V. M in u s s ignindicates decrease in volume. *KHCO 3 mean significantly differentfrom NaH CO3 m e a n , P 0.05.

Fig. 2. Glomerular filtration rate (GFR, A ) a n d u r in e fl ow r a te (B )before (up to 0 min), during (160 min), and after (61270 min)ingestion of NaHCO3 (j) or KHCO3 (r) at a dose of 3.57 mmol/kgb o d y m a s s . U r in e fl o w r a te in th e K H CO3 tr ial was significantly(P 0.05) greater than in the NaHCO 3 tria l between 60 and 180 min.GFR in the KHCO3 trial was significantly (P 0.05) greater than inthe NaHCO3 tria l between 60 and 120 min. Hatched bars indicate the60-min period of HCO3 ingestion. Values are means SE ; n 5.*Significantly different (P 0.05) from preingest ion (20 and 0 m in).Significant difference between trea tmen ts.



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(78 21 eq/min; F ig. 3A ). The fractional excretion ofNa i n cr e a s ed fou r fol d b y 1 2 0 m i n , a n d t h e m e a ncumu lative fra ctiona l excretion was appr oximat ely two-fol d g r e a t e r t h a n b a s el in e a ft e r Na HCO3 ingestion(Fig. 3B ).

I n t h e KHCO3 trial , urine [Na] did not change a ndwa s l o we r t h a n i n t h e Na HCO 3 trial between 60 and270 min (not shown). With KHCO 3 ingestion, U NaV

increased rapidly and was greater than initial levelsb e t we e n 6 0 a n d 1 2 0 m i n a n d t h e n d e c l i n e d t o wa r dinitia l values by 180 min (Fig. 3A ). Between 60 and 120m i n , U NaV w a s g r e a t e r i n t h e K H C O 3 t h a n i n t h e

Na HCO3 trial . There was n o significant chan ge in thefractional excretion of Na (Fig. 3B ).

Potassium. I n t h e N a H CO3 t r i a l, u r i n e [K] r e -

mained unchanged at

10 4

16 meq/l (not shown);excret ion a nd t he fractiona l excret ion of K also did notchange (Fig. 3, C a n d D). In contrast, in the KHCO3trial, ur ine [K] increas ed ra pidly from 77 19 meq/l at120 min to 241 37 meq/l at 270 min. This increasewas a ccompan ied by a sixfold increa se in U KV between120 an d 180 min (Fig. 3C) an d an elevated K fractionalexcretion to 71 12% of the filtered load in th e last 30min of the experiment (Fig. 3D). In th e KHCO3 trial, ofthe 281 meq of K ingested, the increase in ECF K

cont ent only accoun ted for 3%, wher eas n et K flux int otissu es a ccount ed for 37% (Table 3). Over th e 270 min oft h e e xp e r im e n t , i n cr e a s e d (a b ov e b a s a l) UKV a c-counted for 26 5% of the ingested K or 76% of th etotal cumulat ive UKV of 93 16 meq (Table 3).

Chloride. In the NaHCO3 trial, ur ine [Cl] decreased

from 186 16 meq/l at 0 min to 40 7 meq/l at 120m in , w it h n o c h a n ge in C l excretion or fra ctionalexcretion (Fig. 3, E a n d F). In contra st, in th e KHCO3trial , urine [Cl] decreased by only 80 meq/l, from19 7 29 meq/l at 0 min to 119 12 meq/l at 80 min,returning to 173 15 meq/l at 270 min. Despite thedecrease in urine [Cl], the marked increases in UFRand GF R resulted in a significan tly increased rena l Cl

Table 3. N a balance with NaHCO3 ingestion and K

balance with KHCO 3 ingestion at 270 min

Na Balance WithNa HC O3 Ingestion

K Balance WithKHCO3 Ingestion

Na ,m eq

%Ingested

K,m eq

%Ingested

Am ou n t in ge s ted 2 8021 28123

P la s ma con t en t 2 89 21ISF con ten t 12842 73E CF con ten t 15751 5619 93 31Tissu e flu x 30158 149 967 375R en a l e xcr et ion 847 302 9316 346Other effectors 8157 1450 8231 279Tot a l 1000 1000

Values are means SE ; n 5. Not shown is 65 meq of Na

infused with the saline drip. Plasma content, change in arterialplasma content; ISF content, change in interstitial fluid content;ECF content, change in extracellular fluid content. For changes inP la s m a , I S F, a n d E CF con te n ts , m in u s s ig n in dica te s d e cr e a s e.Tissue flux, total wh ole body skeleta l mus cle influx () or efflux () ofNa or K (27); renal excretion, cumulative Na or K excretion;other effectors (gastr ointest inal t ract, eryth rocytes), chan ges in ECFcontent not accounted for. % Ingested, percent ingested Na or K

accounted for by tissue flux, renal excretion, and other effectors.

Fig. 3. Renal ion excretions (UNaV, A; U KV, C; and U ClV, E) and fractional excretions of Na (B ), K (D), and Cl

(F) before (0 min), during (160 min), and after (61270 min ) ingestion of NaHCO 3 (j) or KHCO3 (r) at a dose of3.57 mmol/kg body mass. Hatched bars indicate the 60-min period of HCO3 ingestion. Values a re mea ns SE ; n 5.*Significant ly different (P 0.05) from prein gestion (20 and 0 min ). Significant difference between trea tmen ts.



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e xcr e t ion b et w ee n 6 0 a n d 1 20 m in (F ig . 3E). Cl

fractional excretion did not change significantly ine it h e r t r i a l, a l t h ou g h Cl fractional excretion wasgreater in the KHCO3 t r i a l t h a n i n t h e Na HCO 3 trialbetween 80 and 270 min (Fig. 3 F).

Calcium, Pi, an d la cta te. In both trials, urine [Ca2]

decreased two- to threefold from 3.6 0.6 meq/l at 0min t o between 1 a nd 2 meq/l from 80 an d 270 min, withno difference between t rials. Renal Ca 2 excretion a ndCa 2 fractional excretion did not change from initialvalues (3 1 eq/min and 1.7 0.7%, respectively) ineither t rial, with n o difference between treat ment s.

I n t h e Na HCO3 trial, ur ine [P i] remained unchangedat about 24 4 mmol/l. In the KHCO3 trial, urine [P i]decreased threefold (from 26 13 m mol/l) at t ime 0 t o4.3 1 .6 m m ol /l wit h i n 8 0 m i n a n d r e m a in e d l owthereafter. P i excretion did not change (20 9 mol/min) in either treatment, with no difference betweentrials.

Ur i n e l a c t a t e concentra tion was initially 0.02 0 .0 1 m e q /l in b ot h t r ia ls , a n d in b ot h t r ia ls i t a p -

proached zer o by 270 min (not sh own).[S ID], pH, and [H]. I n t h e N a H C O3 t r i a l , u r i n e[S ID ] i n cr e a se d r a p id ly u n t il 8 0 m in a n d t h e n in -creased slowly until the end of th e experiment (Fig. 4A ).I n t h e K H C O3 trial , urine [SID] increased graduallya n d wa s g r e a t e r t h a n i n i t i a l l y b e t we e n 1 8 0 a n d 2 7 0min, but i t remained 125175 meq/l lower tha n in theNa HCO3 trial .

I n b ot h t r i a ls , t h e m a g n it u d e a n d t i m e c ou r s e o f increase in urine pH were similar, with nadirs reachedat 80 min ; th ere were no differences between tr ials (Fig.4B ). In the Na HCO3 tria l, urine [H

] decreased signifi-cant ly from 354 283 neq/l (t ime 0) to 6.8 0.4 neq/l at270 min, compared with 1,414 1,319 neq/l (t i m e 0)

an d 13.7

3.9 neq/l at 270 m in in th e KHCO3 trial.Urine [SID] (meq/l) was a good predictor of urine [H](neq/l), as shown by the monoexponential curve fit tot h e d a t a ( Fi g . 4C). The lower dotted l ine in Fig. 4 Crepresents the relationship between [H] an d [SID] inth e absen ce of CO2 an d weak acids in th e solut ion (35).The difference between the dotted line and the experi-ment al data represent s the acidificat ion cont ributed byurine P CO 2. The dashed line represen ts th e relationsh ipbetween [H] and [SID] when solution P CO 2 is 40 Torrwith no weak acids present ([Atot ] 0): [H] KC P CO 2/[SI D], wit h u n it s for [SI D] in eq /l (3 5). Th e da sh edline fits t he data well , supporting the assumption t hatu r i n e P CO 2 was similar to arterial P CO 2. The relation-

s h i p a l so s h ows t h a t a ci di fica t i on b y CO 2 wa s p r o-nounced at low a nd negative u rine [SID] (before bicar-b on a t e i n ge s t ion ) a n d m i n or wh en [SI D] wa s 10 0meq/l (after the start of bicarbonate ingestion). Thesmall amount of weak acids present in urine did notcontr ibute subst an tially to the relat ionsh ip (35).

T A , N H 4, an d n et aci d excr eti on . In both trials, there

were large and rapid decreases in urine [TAH CO 3],

U TAHC O3V, and net acid excretion (Fig. 5). Urine [TA

H CO 3] was significan tly decreased from initial values

by 80 min in both trials, with similar m agnitudes andtime course of change (Fig. 5A ). The associated large

and rapid decrease in U TAHC O3

V (Fig. 5B ) represented

a pronounced net excretion of titratable base between80 an d 180 min; th ere was no difference between t rials.

In both trials, urine [NH 4] decreased sevenfold by

100 min, with no difference between trials (Fig. 5D)U NH

4V did not change in either trial (Fig. 5D). U rine

net acid concentration (Fig. 5E) and net acid excretion(Fig. 5F) were quantitatively similar to that for TAH CO 3

, b e c a u s e U NH4V formed only a small (13%)

p r op or t i on of t ot a l a ci d e xcr e t ion . I n t h e Na HCO3trial , an a mount equivalent t o 23 3% of the ingestedb a se w a s e xcr e t ed , w h er e a s i n t h e K H CO3 t r i a l

Fig. 4. Urine strong ion difference concentr at ion ([SID]) (A) , urinepH (B ) , and urine [H] (C) before (0 min), during (160 min), andafter (61270 min ) ingestion of NaHCO 3 (j) or KHCO3 (r) at a doseof 3.57 mmol/kg body mass. Dashed line in C represents relationshipbetween [H] and [SID] in the absence of CO2 in the solution (37).Urine [SID] (A) in NaHCO3 trial was significantly (P 0.05) great erthan in KHCO3 tria l from 80 to 270 min. Monoexponent ial rela tion-ship between urin e [SID] and urine [H] is described by the equat ion[H] 59.168 4.223exp([SID] 0.0122 0.00154) (r2 0.670; P 0.001;n 54). Hat ched bars in dicat e th e 60-min per iod of HCO3 ingestion.Values are means SE ; n 5. *Significantly different (P 0.05)from preingestion (20 and 0 min). Significant difference betweentr e a tm e n ts .



8/12


9/12

In addition, urine [Cl] wa s g r e a t e r t h r o u g h o u t t h eKHCO3 trial . Urine [SID] increased by 175 meq/lgreater in the NaHCO 3 t r i a l t h a n i n t h e KHCO3 trial,a n d t h i s b a l a n ce d t h e d e cr e a s e i n u r i n e [ TAH CO 3]and net acid concentra tion. In general, KHCO3 inges-tion resulted in lower urine [Na ], [K], an d [Ca 2], an dhigher [Cl] tha n in the NaH CO3 trial. Chan ges in CO2did not contribute substantially to urine [H] (see Fig.4C), consistent with the fact that arterial , and hencerenal, P CO 2 (not shown) changed little in both trials.

An increase in urine [Atot ] a l s o c on t r i b u t ed t o t h emeasured urine [H]. In both trials large decreases in[TAH CO 3

] were largely independent of changes inurine [P i], with urine [P i] only accounting for a smallfraction of [TAH CO 3

]. As previously described (8),this suggests tha t there was a n increased excretion of weak a cids and bases, but th eir identity an d contribu-tions are not kn own in t he present stu dy. The contribu-tion of NH 4

to net acid excretion was small (13%),consistent with a previous report of decreased U NH

4V

after KHCO3 an d KCl ingestion (37).

In th e present study, and in t hat by Van Buren et a l .(37), mu ch of the decrease in n et acid excretion wouldbe class ically described as d ue t o increa sed excretion ofH CO 3

. Th is ch a r a c t er i za t i on i s con s is t e n t wit h a napparent 40% reduction in tubular HCO 3

reabsorptionin rats with acute metabolic alkalosis (33) and withstudies showing that loading with KHCO3, N a H C O3,KCl, and NaCl results in decreased rena l HCO3

reab-sorption and decreased urine [H] i n d og s (2 9) a n dhu ma ns (2, 37). In a ddition, t here is a lso evidence thatelectrogenic proton secretion is reduced in rat nephronsas soon as 3 h a fter t he onset of NaHCO 3 loading (24).This is consistent with t he large, tran sient decreases inTA (37) and TAH CO 3

(present study) excretion ob-

served 13 h after K

loading in humans.Water balance. Ingestion of N aHCO 3 r e s u l t e d i n a

prolonged ret ention of fluid with t otal cum ulative ur inevolum e a ccount ing for only 44% of ingest ed volume. Anestimated 56% of ingested Na r e m a i n e d i n t h e ECFcompartment at the end of the experiment (Table 3)consistent with the nearly 1-li ter expansion of ECFV(27). Increa ses in t he delivery of Na, K, and base, i.e.,i n cr e a s ed os m ol a l cl ea r a n c e, t o t h e d is t a l t u b u l es ,wit h ou t con com i t a n t ch a n g e i n GFR, s u g g es t t h a tdecreased tubular fluid reabsorption occurred in asso-ciation with increased distal tubule Na delivery. Theincrease in U FR, h owever, was largely normalized 2 hafter ingestion of th e solution, indicating that there

was a decreased sensitivity of the volume regulatorysystem or some feed-forward mechan ism to preventoveradjust ment in term s of water excretion and U NaV.

In contrast, ingestion of KHCO3 resulted in a rapidand pronounced decrease in plasma volume that wasat tribut ed to an initial ra pid net movement of fluid intothe proximal small intestine to bring intestinal con-tents toward plasma osmolarity, with subsequent ab-sorption of water and K in more dista l portions of th esma ll intestine (27). Despite th e 0.5-liter r eduction inplasma volume, UFR increased two- to threefold moret h an in t h e N a H CO3 t r ia l, a n d t h e r e w e r e r a p id ,

fourfold increases in GFR and excretion of Na, Cl,a n d K.

Th e m a g n i t u d e o f i n c r e a s e i n GFR i n r e s p o n s e t oKHCO3 ingestion appears to be without precedence int h e l it e r a tu r e . O n e s t u dy on h u m a n s r e por t e d n ochan ge in GF R in the second h our after ora l ingest ion ofa small amount (1 mmol/kg body mass) of KCl (37).Modest increases (19 ml/min) in GFR in sheep givenKCl have been reported (4), whereas in rat s a decreasein GFR occurring one or more hours a fter K loadingha s been report ed (6, 7, 40). Also, earlier st udies did notr e p o r t GFR u n t i l a t l e a s t 1 h a f t e r K loading. Fr omFig. 2, it is evident that the increase in GFR was rapidand t ran sient a nd ha d retur ned to preingestion valueswithin 210 min after KHCO3 ingestion was completed.It is difficult to pr ovide a mechanistic explana tion forth e fourfold increa se in GFR in the a bsence of mea sur esof blood pressure, peripheral vascular resistance, andheart rate. I t is not l ikely that KHCO3 ingestion wasassociated with marked increases in blood pressure,given that PV decreased markedly, nor with increases

in vascular resistan ce, given tha t elevated plasma [K

]has vasodilatory effects. The r apidity and magnitu de atwhich th e hyperkalemia ensu ed, compared with ear lierstu dies (9, 30, 37), ma y ha ve indu ced ind irect effects byincreasing r enal blood flow and ther eby contributing t oa n i n cr e a s e i n n e t filt r a t i on p r e ss u r e a n d p e r fu s ionpressure at the level of the juxtaglomerular apparatus.However, it is unk nown if th e chan ges in tubu lar wat erand ion ha ndling were due to the increase in GFR or tot h e i n c r e a s e i n fil t e r e d K ( 7 ) , a n d f u r t h e r s t u d y i srequired to understand the mechanistic relationshipsresponsible for these observations.

N a excretion. I n t h e N a H C O3 t r i a l , t h e r a p i d a n dlarge increases in urine [Na], U NaV, and fra ctionalexcretion accounted for 24% of ingested Na, with theb u l k o f t h e Na r e m a in i n g i n t h e ECF com p a r t m e n t(27). The increase in U NaV c a n b e a t t r i b u t e d t o t h emodest increases in GFR and increased Na deliverywith decreased proximal t ubule Na reabsorption. Theprimary m echan ism for reduced proximal tubule Na

reabsorption is th rough inh ibition of proxima l tu bularNa-K-ATPase (2, 22), resulting in increased Na

(an d wat er) delivery to the dista l tubu les. There is alsoe vi de n ce t h a t a cu t e , t r a n s i en t e le va t i on s i n d ie t a r yNa i n d u ce a n a t r i u r e s is b y a d op a m i n e-m e d ia t e ddecrease in proxima l tubule Na-K-ATPa se a ctivity (1).

In the KHCO3 trial the hyperkalemia was associated

with increased renal U Na

V despite th e 15% reductionin plasma volume and decrease in plasma [Na]. Hyper-k a l em i a h a s b ee n s h own t o i n h i bi t Na a n d w a t e ra b s or p t i on b y t h e p r ox im a l t u b u l e, r e s u lt i n g i n adiuresis and nat riuresis (6, 7) without cha nge in plasmarenin (30, 37, 38) and atrial natriuretic peptide (37).I n cr e a s ed GFR wa s a s s oci a t ed wit h e le va t e d d is t a lt u b u l e Na d e li ve r y wit h m i n im a l i n cr e a s e i n Na

fractional excretion. There appears to be minimal evi-dence for decreased Na reabsorption in the diuretica n d n a t r i u r e t i c r e s p o n s e s t o KHCO3 ingestion. Thisfinding is in contr ast t o the n at riuresis th at occurs with



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KCl ingestion (38), indicating that the accompanyinganion plays a role in modulating tubular excretion andreabsorption of Na (22). The later decline in renalU NaV (fr om 1 20 m in on w a r d) i s a t t r ib u t ed t o t h es t r on g a n t i n a t r i u r et i c a c t ion of a l dos t e r on e a n d t h eensuing increase in tubular Na reabsorption (31, 37,38, 41). This effect and associated decreases in GFR,UFR, and Cl excretion are consistent with the effectsof aldosterone occurring 12 h after i t begins to in-cr e a s e i n t h e b lood (1 2, 4 1). I t i s c on cl u de d t h a t aK-stimulated natriuresis was responsible for the ob-served hyponatremia.

K excretion. Na HCO3 ingestion resulted in a small,alth ough not sta tistically significant , increase in U KV,a tendency (Fig. 4) that was associated with a modesthypokalemia. A tendency (P 0.1) toward increasedU KV i s con s is t e n t wit h i n cr e a s ed d e li ve r y a n d n e treabsorption of Na, but not Cl, at t he distal tubules;this tendency establishes a negative electrochemicalgradient t ha t favors modest increases in UKV (16, 39).Alkalosis has also been reported to stimulate Na-K-

ATPase-mediated uptak e of K

into principal cells,resulting in enhanced K secretion (34). An increaseddelivery of HCO3

to the distal nephr on, in the presenceof i n cr e a s ed a l dos t e r on e , m a y a l so s t im u l a t e U KVdu ring a lkalosis (34).

I n t h e KHCO3 tr ial, increased excretion of K abovebasa l levels accoun ted for 26 5% of ingested K. Overth e cour se of the experiment, total U KV accoun ted for34 6% (about 1.2 mm ol/kg) of ingested K, represent-ing about 17% of the n orma l kidneysda ily capa city of 7mmol/kg (31). The incomplete renal excretion of allingested K a g r ee s wit h t h e ob s er v a t ion t h a t a b ou t64% of ingested K had entered cells by 270 min andwas thus removed from the ECF and the circulatorysystem (27).

The rapid, fivefold increase in renal U KV was bipha -sic in t ime cour se, peaking at 90 min before decreasing(Fig. 3C), and paralleled increases in plasma [K] a n daldosterone concentra tion (Fig. 1). The early rise inU KV preceded the kaliuretic action ofincreased plasmaaldosterone concentra tion but coincided with the in-crease in filtered K load, perhaps indicating a directkaliuretic effect of increased plasma [K] (3 0). I ncontrast, the fractional excretion of K progressivelyincreased over t ime, peaking at 71 12% of the filter edload at 270 min, consistent with the peak effects of aldosterone occurr ing 1 2 h after it increases (12, 41).

These results are consistent with previous studies of K loading in h uma ns (9, 30, 37, 38) and other an imals(3, 6, 7, 21, 32, 41). It is likely tha t elevat ed plasm a [K]and aldosterone concentration independently contrib-ut ed to th e kaliur esis (9, 31) by increasin g principal cellNa-K-ATPase activity (34) and intra cellular [K] inthe distal tubule and cortical collecting duct (13, 15).Also, the presence of anions that are relatively imper-meant to distal tubule reabsorption (such as bicarbon-ate and sulphate) increases luminal electronegativityand may h ave contributed to th e increase in K secre-tion (39). An increased flow of fluid through the distal

tubule and cortical collecting duct also stimulates K

secretion by thes e segment s (16, 26).Cl excretion. I n t h e N a H CO3 t r ia l, a s m a y b e

expected with increased HCO 3 delivery to the t ubules,

th ere occurr ed a 146 meq/l decrease in u rin e [Cl] an d amodest increase (not sta tistically significan t but a ppear -ing to be of physiological importance) in tubular Cl

reabsorption (Fig. 3F). This response is similar to thatseen occurring after acute lactate loading caused byh i gh -i n t en s it y e xe r ci se (2 8); t h e r e a p p ea r s t o b e apreferential reabsorption of Cl over H CO3

and lac-t a t e. Overall , though, the NaHCO3 load had only as m a ll e ffe ct on r e n a l Cl t r a n s p or t , s im i la r t o t h eabsen ce of effect of Na Cl loadin g on ren al Cl excretion(17, 37).

The rena l Cl response to KHCO3 ingestion, h owever,is in ma rked contra st to that seen in th e NaHCO3 trial .Cl excretion markedly increased equimolar with theincreas ed excret ion of Na, resulting in similar cumu la-tive excretions of Cl a n d N a. Similar responses toKHCO3 loading in humans have previously been re-

ported (37), a nd increased HCO3

delivery has beensuggested to reduce net Cl reabsorption by th e proxi-mal tubules and increase Cl excretion (37). The ab-sence of a similar result in the NaHCO 3 t r i a l m a y b eexplained by the absence of the rapid and very largei n c r e a s e i n GFR s e e n i n t h e KHCO 3 t r i a l . Th u s t h emarked increases in both Cl a n d N a excretion seenafter KHCO3 ingestion appear to be associated withmecha nism s for acute regu lat ion of plasm a [K] (10, 25,37). The decrease in Cl excretion late in the experi-ment (180270 min) was similar t o that seen for Na

and is consistent with Na-dependent Cl absorptionmechan isms responding to elevated plasma aldoste-rone concentr at ion (10, 17).

R en al Ca2

an d Pi regulation. Th e i n ge s t ion of Na HCO3 a n d KHCO3 did n ot significan tly affect rena lCa 2 a n d P i excretion. In both trials, the decreases inurine [Ca 2] and [P i] were due solely to the accompany-ing diuresis, consistent with the absence of significan tcha nge in plasma Ca 2 cont ent (27).

Im pli cat ion s for exercis e per form an ce. Na HCO3 load-ing is widely practiced in human and equine athleticcom p e t it i on a s a m e a n s of r e d u ci n g t h e s e ve r it y of extra- and intracellular acidosis resulting from theperforma nce of high-inten sity exercise (19). Ind eed, th edose of NaHCO3 a d m in i s t er e d i n t h e p r e se n t s t u d yconsistently results in performance-enhancing effectsi n h u m a n s ( 1 9 ) . I t i s a l s o n o t e wo r t h y t h a t Na HCO 3

loading resulted in an

1-liter expan sion of plasmavolume that persisted in excess of 3 h after ingestion ofthe solution. This result indicates that the gastrointes-t in a l t r a ct m a y b e u s e d a s a r e se r voir of r e a d ilyavailable water an d Na for m aint aining extra cellularvolume during prolonged exercise. On the negativeside, there was a twofold increase in UFR during thefirst 2 h after ingestion that may compromise exerciseperformance.

High-intensity exercise results in the rapid loss of K

from contra cting skeletal m uscle, a nd the resultingdecrease in intracellular [K] is thought to contribute



11/12

to skeletal muscle fatigue (see Ref. 27). The rationalefor providing su bjects with oral KHCO3, a t a d o s ee q u iv a le n t t o t h e p e r for m a n c e -e n h a n c in g e ffe ct of Na HCO3, w a s t w ofold . T h e fi r st w a s t o p r ovi de asimilar magnitu de alkalosis to offset exercise-inducedacidosis, with the idea that K being predominantlyintracellular would provide further protection againstintr acellular acidosis. The second was to provide a ddi-tional K to skeletal mu scles so as to better ma intainintr acellular [K] and delay the onset of fatigue in theface of contraction.

However, the results of the present study indicatet h a t KHCO3 loading should not be considered for theenhancement of exercise performance. Ingestion of thisquant ity of K poses safety concerns, both at rest andparticularly if subjects are contemplating exercise.Ingest ion of more th an 150 mm ol (about 16 g) of KHCO3r e s u l t s i n a r a p i d i n c r e a s e i n p l a s m a [ K] t h a t m a yrequire prompt treatment for hyperkalemia (see Ref.27). Two hours after ingestion of KHCO 3, subjectsmaintained an average plasma [K] of about 6 meq/l,

which, with high-intensity exercise, could result inlife-thr eatening increases in plasma [K]. Also, it islikely that the rapid and pronounced decrease in plasmavolume th at occurred with KHCO3 ingestion may im-pose additiona l stress on th e cardiovascular an d intest i-na l systems dur ing exercise.

Conclusions. Renal responses to ingested NaHCO3a n d K H CO3 solutions are more rapid and of greatermagnitude than previously appreciated. In both trials,excreted Na a n d K accounted for 2540% of theingested ion an d, in the KHCO 3 trial, cumulative urinevolume over 270 min equaled the ingested volume load.I n b ot h t r ia ls , t h e G F R a n d U F R r e sp on s es w er etr ans ient an d largely norma lized by 210 min postinges-

tion. The neu ral an d cellular mechanisms for t he ra pidu p - a n d d ow nr egu la t ion of G F R a n d U F R in t h eNa HCO3 trial are not well understood. The rapidity ofthe downregulation suggests either that , after sometime, the regulatory systems become tolerant of theremaining fluid imbalance or that there may be feed-forward mechanisms for preventing overadjustment offlu i d a n d Na balance. In the KHCO3 compared witht h e N a H C O3 trial, renal ion excretions occurred withgreater rapidity, were of greater magnitude, and re-sulted in an increased osmotic clearan ce. In both trials,increases in base excretion were sustained until theend of the experimental period. It is also noteworthytha t, although the plasma acid-base disturbances ha dma rkedly different physicochemical origins (27), th erenal acid-base responses were similar with respect toexcretion of base. The rapidity and magnitude withw h ich t h e k id n ey s r e sp on d ed t o t h e N a H C O3 a n dKHCO3 loading demonstr at e th eir capacity, and physi-ological importance, for restoring body fluid homeosta-sis in the face of large, acute disturbances in water, ion,an d a cid-base ba lance.

This study was supported by t he Na tura l Sciences and Engineer-ing Research Council of Canada and the Medical Resear ch Council ofCa n a d a . G . J . F . H e ig e n h a u s e r is a Ca r e e r I n v e s tig a to r w ith th e

Hear t an d Stroke Foundat ion of Onta rio. L. C. Lands is a Ch ercheur-clinicien with th e Fonds de la Recherche en San te du Quebec.

Address for reprint requests a nd other correspondence: M. I .Lindinger, Dept. of Huma n Biology & N utr itional Sciences, Univ. ofGuelph, Guelph, ON, Cana da N1G 2W1 (E-mail: [email protected]).

Received 16 February 1999; accepted in final form 15 October 1999.

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ingestão de bicarbonato aumenta excreção eletrolítica

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