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At least 19 recordsLinked to original sources
PubMed1978

Studies on the tubulo-glomerular feedback system in the rat. The mechanism of reduction in filtration rate with benzolamide.

The specific mechanism whereby superficial nephron glomerular filtration rate (sngfr) is reduced after the administration of benzolamide, a carbonic anhydrase inhibitor with a primary inhibitory effect in the proximal tubule, have been examined by measuring pertinent pressures, flows, and glomerular permeabilities in the hydropenic Munich-Wistar rat, a strain with surface glomeruli. Because benzolamide decreases absolute proximal reabsorptive rate, the rate of delivery of tubular fluid to the distal nephron should be at least transiently increased and may reduce sngfr by activating the tubulo-glomerular feedback system. Sngfr fell from 29.2+/2.0 to 2.1+/3.1 nl/min (P less than 0.01) after benzolamide (group 1), a percentage reduction equal to kidney glomerular filtration rate and similar to sngfr obtained in collections from distal tubules. Separate studies (group 2) revealed that if transient increases in distal nephron delivery were prevented by insertion of a long oil block in proximal tubules before control, the decrease in sngfr was prevented (30.3+/1.0 vs. 30.3+/1.8 nl/min, P greater than 0.9). In paired "unblocked" nephrons in the same rats, sngfr fell in group 2 (33.0+/1.0 vs. 25.2+/2.3 nl/min, P less than 0.01). In "blocked" nephrons in which sngfr reduction was prevented, the rate of fluid leaving the proximal tubule increased from 16.9+/ to 23.1+/1.0 nl/min (P less than 0.01). In group 1 studies in which sngfr fell and transient increases in flow out of the last segment of the proximal tubule (distal delivery) (approximately equal to 8 nl/min) were not prevented, steady-state distal delivery was unchanged by benzolamide (13.9+/1.1 vs. 14.2+/2.2 nl/min). Also, sngfr returned toward control, pre-benzolamide values, when a proximal oil block was placed for 15 min and the rate of distal delivery reduced after benzolamide administration, which suggests that this activation was reversible. These data suggest that activation of tubulo-glomerular feedback by transient increases in distal delivery was responsible for decreases in sngfr. Analysis of all determinants of glomerular ultra-filtration revealed that the efferent mechanism leading to reduced sngfr after benzolamide was decreased nephron plasma flow (101+/13 vs. 66+/13 nl/min, P less than 0.01). Hydrostatic pressure and the glomerular permeability coefficient did not contribute to reductions in sngfr with benzolamide. Because the rate of distal delivery remained constant in spite of large changes in both sngfr and absolute proximal reabsorptive rate, it is suggested that the rate of distal delivery may be the physiologic entity that is regulated by the tubulo-glomerular feedback system via alterations in sngfr.

Animals↗
PubMed1979

Microelectrode determination of pH and PCO2 in rat proximal tubule after benzolamide: evidence for hydrogen ion secretion.

Previous micropuncture studies supporting hydrogen secretion as the mechanism of bicarbonate reabsorption have relied on the demonstration of an acid disequilibrium pH in the proximal tubule after systemic administration of a carbonic anhydrase inhibitor. Previous calculations of disequilibrium pH, however, have involved the necessary assumption that PCO2 in the proximal convoluted tubule was equal to arterial blood PCO2. This assumption can no longer be supported in view of the recent demonstration that the PCO2 in proximal and distal tubular fluid exceeded arterial blood by approximately 25 mm Hg. The purpose of the present study was to determine directly pH and PCO2 with microelectrodes in both the early and late segments of the accessible proximal tubule of nine Sprague-Dawley rats before and after administration of benzolamide (2.0 mg/kg/hr, i.v.). In the early proximal tubule, pH decreased significantly after benzolamide administration from 6.98 +/- 0.03 to 6.62 +/- 0.03 pH U (P less than 0.001), and PCO2 also decreased from 65.1 +/- 1.2 to 59.3 +/- 1.4 mm Hg (P less than 0.005). In the late proximal convoluted tubule, pH did not change after benzolamide (6.75 +/- 0.02 to 6.77 +/- 0.02), but PCO2 decreased significantly (64.3 +/- 1.5 to 57.7 +/- 1.6) (P less than 0.01). We conclude: (1) the fall in both pH and PCO2 in the early proximal tubule indicates that carbonic acid, not carbon dioxide accumulates after inhibition of luminal carbonic anhydrase; (2) although PCO2 also decreased in the late proximal tubule, unlike the early segment, pH was unchanged after benzolamide administration, perhaps as a result of increased bicarbonate delivery; and (3) PCO2 in vivo was significantly greater than was systemic arterial PCO2 before and after benzolamide administration in both the early and late proximal convoluted tubule. These findings lend support to the view that bicarbonate reabsorption in the proximal convoluted tubule occurs, in part, by hydrogen secretion.

Animals↗
PubMed1978

Effect of benzolamide on luminal pH in proximal convoluted tubules of the rat kidney.

Luminal pH in early and late proximal tubules was recorded continuously with antimony microelectrodes before and during carbonic anhydrase inhibition. Following i.v. application of benzolamide (25 mumol/kg BW), luminal pH decreased almost immediately in early proximal tubules (deltapH--0.42 +/- 0.06SEM), but increased in late proximal tubules (deltapH +0.27 +/- 0.06). Urinary pH increased (deltapH + 1.6 +/- 0.16) after a delay of some 30 s. Similar results, i.e. decrease of pH in early and increase of pH in late proximal tubules, were obtained, when benzolamide containing solutions were microinfused into early proximal tubules or superfused on the nephron surface. In contrast, luminal pH decreased in late proximal tubules, when benzolamide was microinfused into the same nephron segment. The decrease of luminal pH indicates inhibition of luminally active carbonic anhydrase, leading to delayed buffering of secreted hydrogen ions. The increase of luminal pH in late proximal tubules may be attributed to several factors including increased delivery of bicarbonate, impaired bicarbonate exit at the antiluminal membrane and decreased hydrogen ion formation in the tubular cell due to inhibition of cellular carbonic anhydrase.

Animals↗
PubMed1975

CO2 retention as a basis for increased toxicity of salicylate with acetazolamide: avoidance of increased toxicity with benzolamide.

Two carbonic anhydrase inhibitors, acetazolamide and benzolamide, are capable of increasing the toxicity of sodium salicylate in mice. Beginning at about 2 mg/kg, each of the inhibitors, in combination with a fixed (400 mg/kg) dose of salicylate, generates a dose-mortality curve that reaches a plateau at about 60% deaths at 6 to 8 mg/kg. This effect can be duplicated by 8 to 10% inspired CO2. It appears that the respiratory acidosis secondary to the inhibition of red cell carbonic anhydrase is responsible for the increased toxicity; earlier work by others shows that acidosis increases the concentration of salicylate in the brain. In the treatment of salicylate poisoning by carbonic anhydrase inhibitors, the goal is to alkalinize the urine and increase the excretion of salicylate. With the newer inhibitor, benzolamide, it is possible to dissociate the respiratory acidosis from the renal effect. Maximal alkalinization of the urine is possible with a dose (about 1 mg/kg) below that which generates a respiratory acidosis. With this dose, there is no increase in the early toxicity of salicylate.

Acetazolamide↗
PubMed1975

Clarification of the site of action of chlorothiazide in the rat nephron.

The saluretic effect of the thiazide diuretics has been attributed to inhibition of sodium reabsorption in the distal nephron of the kidney. Recent micropuncture studies have shown, however, that chlorothiazide administration can also inhibit sodium reabsorption in the proximal convolution. To clarify the site of the saluretic effect of chlorothiazide, these micropuncture studies examined the effect of chlorothiazide on chloride transport in the nephron. The effect of chlorothiazide on chloride transport was studied because chlorothiazide's effectiveness as a saluretic is largely due to its ability to enhance sodium chloride excretion; if only changes in sodium transport are examined, it would be then difficult to determine if sodium as bicarbonate or as chloride is affected, since chlorothiazide can inhibit carbonic anhydrase. One group of rats was studied before and after 15 mg/kg per h chlorothiazide. For comparison, another group of rats was studied before and after 2 mg/kg per h benzolamide, a carbonic anhydrase inhibitor. Fractional chloride delivery from the proximal tubule was similarly increased in both groups from 59.4 to 71.0% by chlorothiazide administration, Pless than 0.0001, and from 54.3 to 68.2% by benzolamide administration, P less than 0.001. The increased delivery very of chloride from the proximal tubule was largely reabsorbed before the early distal tubule as fractional chloride delivery to this site increased only from 5.08 to 7.40% after chlorothiazide administration, P less than 0.001, and from 4.50 to 6.29% after benzolamide administration, P less than 0.01. Benzolamide had no effect on chloride reabsorption in the distal convoluted tubule. However, chlorothiazide administration resulted in a marked decrease in distal tubular chloride reabsorption, the fraction of filtered chloride present at the late distal tubule incresing from 1.24 to 6.25%, P less than 0.001. Fractional chloride excretion in the urine increased from 0.29 to 3.44%, P less than 0.001, after chlorothiazide, but did not change after benzolamide. The influence of chlorothiazide on proximal chloride transport presumably is related to its ability to inhibit renal carbonic anhydrase. However, it is not the effect of chlorothiazide in the proximal convolution but rather its effect in the distal convoluted tubule which is primarily responsible for its ability to be an effective saliuretic.

Animals↗
PubMed1979

Mode of stimulation by injection of cyclic AMP and external acidification of the sodium efflux in barnacle muscle fibres.

1. A study has been made in single barnacle muscle fibres of the effect of micro-injected pure protein kinase inhibitor (PKI) on the response of the Na efflux to injection of cyclic AMP and external acidification. 2. (i) Injection into fibres of 1.6 x 10(-4) M-pure PKI is without effect on the resting Na efflux. (ii) Injection of 1.6 x 10(4) M-pure PKI before 0.03 M-cyclic AMP causes a marked reduction in the magnitude of the response of the Na efflux to the nucleotide. The same is true when 10(-4) M-cyclic AMP is injected after PKI. (iii) Injection of partially pure catalytic subunits causes a sustained stimulation of the ouabain-insensitive Na efflux, which is almost completely reversed by injecting PKI. (iv) Injection of 100 mM-EGTA before PKI fails to alter the lowered response of the ouabain-insensitive Na efflux to injection of 10(-4) M-cyclic AMP. (v) Ouabain (10(-4) M) when applied following the injection of 10(-4) M-cyclic AMP causes a drastic fall in the stimulated Na efflux. 3. (i) Injection of 1.6 x 10(-4) M-pure PKI before or after external acidification fails to abolish or reduce the stimulatory response to acidification. (ii) Injection of 1.6 x 10(-4) M-pure PKI before acidification practically abolishes the response of the ouabain-insensitive Na efflux to 0.03 M-cyclic AMP in the presence of acidification. (iii) Radioimmunoassay of total cyclic AMP and cyclic GMP content in single fibres before and after acidification shows no appreciable alteration in nucleotide content following acidificiation. (iv) Injection of 100 mM-EGTA before acidification enhances the stimulatory response to acidification. (v) External application of Dantrolene (10(-5) M) fails to alter the size of the stimulatory response to acidification. 4. (i) Prior external application of 5 x 10(-4) M-benzolamide results in a marked reduction in the magnitude of the response of the ouabain-insensitive Na efflux to the injection of 3 x 10(-4) M-cyclic AMP. (ii) Benzolamide totally abolishes the response of the ouabain-insensitive Na efflux to the injection of catalytic subunits. 5. The evidence brought forward is compatible with the view that (a) The mechanism by which cyclic AMP stimulates the Na efflux involves activation by cyclic AMP of the cyclic AMP-dependent protein kinase system, and hence release of the catalytic subunit, and (b) the mechanism by which external acidification leads to stimulation of the Na efflux involves activation of a benzolamide-sensitive system, possibly carbonic anhydrase, rather than the adenyl cyclase system. The actions of cyclic AMP and catalytic subunits on the Na efflux are closely linked to activation of the benzolamide sensitive system.

Animals↗
PubMed1979

Study of factors which modify the development of norepinephrine-induced acute renal failure in the dog.

Previous studies have demonstrated that the fall in inulin clearance which occurs 3 hours after the intrarenal administration of norepinephrine can be markedly attenuated by the prior administration of intrarenal prostaglandin E2 (PGE). Since in the previous studies PGE led to a marked increase in both renal blood flow and solute excretion, we designed the present series of experiments to investigate whether an increase in renal blood flow, solute excretion, or other factors were responsible for the protective effect in the norepinephrine model. Two renal vasodilators, bradykinin and secretin, were evaluated initially. Bradykinin administration prior to norepinephrine administration had a protective effect similar to that previously found with PGE, whereas secretin did not. Both of these vasocilators increased renal blood flow to the same degree, but only bradykinin increased urine flow and solute excretion. The fall in inulin clearance 3 hours after the administration of norepinephrine was also attenuated by two diuretics (mannitol and furosemide) which tended to increase renal blood flow. In contrast, two natriuretic agents, which are also renal vasoconstrictors (chlorothiazide and benzolamide), had no protective effect. Further, chlorothiazide and benzolamide obviated the protective effect of bradykinin. These studies demonstrate that there are several types of pharmacologic agents which can modify the magnitude of renal functional impairment resulting from extreme renal ischemia. Although the mechanism of the protective effects remain unclear, the findings are compatible with the view that the protective effect noted with PGE, bradykinin, mannitol, and furosemide may be related to an increase in osmolar excretion which occurred with administration of each of these agents. This potentially salutory effect (increased osmolar excretion), however, could be overcome by an agent (e.g., chlorothiazide or benzolamide) which also increased renal resistance prior to the administration of norepinephrine.

Acute Kidney Injury↗
PubMed1977

Postcapillary changes in blood pH in vivo during carbonic anhydrase inhibition.

A rapidly responding stopped-flow glass pH electrode apparatus was used to investigate pH changes in blood in vivo after it exits from an exchange capillary. Arterial blood was drawn from anesthetized animals through the apparatus. Temperature and pH of the blood in the electrode chamber were continuously recorded, both during withdrawal and after flow was stopped. Blood pH did not change after stopping flow in control experiments. When benzolamide (2 mg/kg) was given to inhibit carbonic anhydrase activity available to plasma (e.g., due to lysis) while having less effect on intracellular activity, pH increased 0.02-0.04 (t1/2 approximately 8 s) after stopping flow. Administration of acetazolamide (50 mg/kg) resulted in pH decreasing 0.07-0.10 (t1/2 approximately 15 s) after stopping flow. Ventilation for 1 min with N2 resulted in an increased rise in pH for the benzolamide-treated animals but a decreased fall in pH for the acetazolamide-treated animals. These shifts in arterial blood pH after gas exchange are largely due to disequilibrium of [H+] between red cells and plasma at the end of the pulmonary capillary.

Acetazolamide↗
PubMed1975

Effect of ouabain on cerebrospinal fluid formation after carbonic anhydrase inhibition.

The effect of ventriculo-cisternal perfusion of ouabain was determined on CSF production after inhibition of carbonic anhydrase by benzolamide in cats. An additional decrease in CSF formation was observed by combination of i.v. benzolamide and intraventricular ouabain. However, the effect of the combined drugs was less than the sum of the effects of the drugs given individually. It is concluded that the reduction of the CSF production by ouabain is probably partly due to its effect on Na-K exchange (through inhibition of Na-K-activated ATPase) and partly due to its effects on Na+ transport coupled to anion transport mediated by carbonic anhydrase.

Animals↗
PubMed1992

Simultaneous measurement of intracellular and extracellular carbonic anhydrase activity in intact muscle fibres.

The presence and properties of membrane-bound carbonic anhydrases have been difficult to establish with conventional enzymological and immunohistochemical techniques. We have therefore studied carbonic anhydrase (CA) activity in single intact crayfish muscle fibres by superfusing them alternately with a 4-(2-hydroxyethyl)-1-piperazine-ethanesulphonic acid (HEPES)-buffered and a 5% CO2/HCO3(-)-buffered solution (pH of both solutions 7.4) while recording the intracellular pH (pHi) and extracellular surface pH (pHs) with H(+)-selective microelectrodes. In order to prevent regulation of pHi, Na+ ions were replaced with N-methyl-D-glucamine. Application of the CO2-containing solution produced a fast fall in pHi coupled with a marked (0.5-0.8 pH units) transient increase in pHs. Submicromolar concentrations of acetazolamide (AA) and benzolamide (BA) immediately blocked the pHs transients. A concentration of 8 x 10(-8) M (both compounds) reduced the response by 50%. A more prolonged application of BA and AA at concentrations of 10(-7) M and higher slowed the CO2-induced fall in pHi, which attained a rate corresponding to uncatalysed intracellular CO2 hydration at an AA concentration of 10(-4) M. The effect of BA and AA on the pHi changes developed with a time constant of 25 +/- 4 min and 7.6 +/- 1.5 min respectively, indicating that BA is less permeant than AA. CNO- ions (5 x 10(-4) M) had little effect on the CO2-induced pHs and pHi changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1991

Renal carbonic anhydrase inhibition reduces high altitude sleep periodic breathing.

The efficacy of carbonic anhydrase (CA) inhibitors in amelioration of periodic breathing during sleep at high altitude is not fully understood. Although CA is present in a number of tissues, we hypothesized that selective renal CA inhibition without physiologically important inhibition of other tissue CA, may be sufficient alone by its generation of a mild metabolic acidosis to stimulate ventilation and prevent periodic breathing. We studied benzolamide (3 mg/kg), a selective inhibitor of renal CA, in 4 climbers on ventilation and ventilatory responses at sea level and on arterial O2 saturation (SaO2%) and periodic breathing during sleep at altitude. At sea level, ventilation increased and PaO2 rose accompanied by a mild metabolic acidosis. The isocapnic hypoxic ventilatory response was unchanged but the hyperoxic hypercapnic ventilatory response rose 40%. At high altitude (4400 m), daytime SaO2% improved from 81 to 85 and venous plasma HCO3- fell from 18.9 to 14.8 mM. During sleep, mean SaO2% rose from 76 to 80 and periodic breathing decreased 75%. We conclude that metabolic acidosis occurring with all CA inhibitors is one of the major stimulant actions of these drugs on ventilation while awake and during sleep at high altitude.

Acidosis↗
PubMed1976

Potassium secretion by the decending limb or pars recta of the juxtamedullary nephron in vivo.

Potassium reabsorption by the juxtamedullary nephron up to the hairpin turn was studied by the micropuncture technique in the exposed renal papilla of rats. In 18 nondiuretic rats, the fraction of filtered potassium remaining at the end of the desdending limb averaged 113 +/- 9%, indicating either that potassium is not reabsorbed by the juxtamedullary proximal tubule and descending limb or that potassium is reabsorbed and secreted in those segments. Furosemide, a drug which inhibits NaCl reabsorption in the ascending limb downstream from the descending limb, significantly decreased the potassium remaining at the end of the descending limb from 106 +/- 12 to 72 +/-11% in seven rats. Benzolamide, a drug which inhibits reabsorption of NaHCO3 and water in the proximal tubule upstream from the descending limb significantly increased the potassium remaining from 103 +/- 13 to 177 +/- 32% in eight rats. These findings support the hypothesis that in the rat, potassium is normally reabsorbed by the proximal convoluted tubule and secreted in the pars recta or descending limb of the juxtamedullary nephron.

Absorption↗
PubMed1976

Effect of intraluminal bicarbonate and chloride on fluid absorption by the rat renal proximal tubule.

In order to study mechanisms of fluid transport in the rat renal proximal convoluted tubule, the effects of large variations in intraluminal HCO3- and Cl- concentrations were measured by microperfusion techniques. No differences in rates of fluid transport were found when intraluminal HCO3- was varied from 4 to 30 mEq/liter and Cl- from 146 to 120 mEq/liter. Inhibition of H+ secretion with benzolamide had no effect on fluid absorption when little or no HCO3- was present in the lumen, but did reduce fluid transport when 25 mEq of HCO3- was present. If several different mechanisms are responsible for proximal fluid transport, such as nonelectrogenic active NaHCO3 transport, passive chloride diffusion and active sodium transport linked to H+ secretion, the above observations imply that they all operate at approximately the same rate, since the dominant driving force would have been different with each perfusion solution. The data seem more compatible with the view that active sodium transport is the major driving force for fluid absorption in the proximal tubule, that this is not linked to H+ secretion and that anions modify the rate of absorption only to the degree that they are able to accompany sodium across the epithelium. An additional observation was that absorption of isotonic NaCl was very slow in short segments of tubule, as compared to HCO3--containing perfusion solutions. Although the mechanism is uncertain, these data suggest that a finite amount of intraluminal HCO3- is necessary for optimal proximal fluid transport.

Animals↗
PubMed1975

Transmembrane exchange of chloride with bicarbonate ion in mammalian red blood cells: evidence for a sulphonamide-sensitive "carrier".

1. It is well known that red blood cells suspended in isotonic NH4Cl solution swell because penetration of NH3 induces a transmembrane exchange between Cl-o and OH-i(or HCO3-i). The rate of swelling thus depends on the speed of the transmembrane exchanges and on the amount of anions available for exchange. 2. It has been demonstrated in experiments carried out in a CO2-free medium that OH-ions are poorly permeating whereas the permeability for HCO3-is very high. Thus the rate of swelling is largely dependent on the intracellular HCO3-concentration. In this context the well-known inhibitory effect of sulphonamides upon swelling can be interpreted, and always has been until now, as being due to the inhibitory action of the drug on the intracellular carbonic anhydrase. However, this inhibitory effect could also result from a direct action of the drug on the transmembrane exchange; it would explain why under conditions of total carbonic anhydrase inhibition we have shown that the inhibition of swelling is far from maximal. 3. A direct experimental evidence of such an effect of carbonic anhydrase inhibitors on the transmembrane exchange of Cl-with HCO3- was obtained with benzolamide (Cl 11,366), Cl 13,580 and ethoxzolamide. Surprisingly enough, however, acetazolamide (Diamox) does not affect the transmembrane exchange process. 4. The inhibitory effect of sulphonamides on HCO3-transport process is discussed in terms of an interaction of the drug with a transport system common to HCO3- and organic anions.

Acetazolamide↗
PubMed1976

Early postglomerular plasma concentrations of chloride, sodium, and inulin in the rat kidney.

Sodium, chloride, and inulin concentrations were measured in plasma collected from the terminal portions of long efferent vessels at the subcapsular surface of the rat kidney. Sodium concentration equaled and the concentrations of chloride and inulin were less than those in peripheral plasma. During benzolamide infusion, chloride concentration equaled while inulin concentration remained less than in peripheral plasma. In free-flow micropuncture samples collected randomly during control conditions, chloride concentration rose rapidly in the early proximal tubule and then remained elevated and constant throughout the remainder of the proximal tubule accessible to micropuncture. These experiments indicate that normally tubular reabsorbate low in chloride and inulin is added to the blood traversing the early postglomerular vessels before reaching the kidney surface. Bases on the analyses of proximal tubular fluid, this type of reabsorbate appears available only from the early proximal tubular segment. We conclude that a close functional relationship exists between the first segment of the proximal tubule and the early postglomerular blood supply characteristic of the superficial cortical nephron.

Animals↗
PubMed1992

Luminal pH in the amphibian distal tubule: effects of carbonic anhydrase and carbonic anhydrase inhibitors.

To better delineate acid-base transport properties in the distal tubule (DT) of Necturus in vivo, we 1) studied the effects of peritubular (pt) isohydric increase of PCO2 and [HCO3-]pt on luminal pH (pHlu), and 2) measured the steady-state pHlu under various experimental conditions. The experiments were carried out on initial (DTi) or distal (DTd) loops of the DT in control state and then during intravenous infusion of carbonic anhydrase (CA) or CA inhibitors (CAI). In control state, isohydric increase of PCO2 and [HCO3-]pt results in transient acidification of the DTi lumen, whereas in DTd lumen the same maneuver yields sustained (plateau) acidification. Under systemic infusion of CAI, isohydric increase of PCO2 and [HCO3-]pt lowers pHlu (sustained fall of pHlu) in DTi and DTd, whereas under CA infusion both segments exhibit only transient acidification. During intravenous infusion with benzolamide DTi steady-state pHlu falls, suggesting that this maneuver inhibits a functional luminal CA, in contrast to the DTd, whose pHlu remains unaltered. Intravenous infusion of CA significantly increases steady-state DTd pHlu; by contrast, steady-state pHlu in DTi does not change. These data are consistent with the presence of functional luminal CA in the DTi, whereas the DTd segment lacks the luminal enzyme.

Acetazolamide↗
PubMed1979

Volume expansion-induced alterations in proximal tubule chloride gradient in the rat.

To elucidate the mechanisms by which acute volume expansion (AVE) induces a decrease in proximal tubule transepithelial chloride gradient, male Sprague-Dawley rats were studied before and after AVE with Ringer lactate. In group 1, after AVE equivalent to 10% body wt, there were decreases in both tubule fluid to plasma inulin ratio ((TF/P)In) (from 2.28 +/- 0.10 to 1.57 +/- 0.05) and tubule fluid to ultrafiltrate chloride ratio ((TF/UF)Cl) (from 1.25 +/- 0.02 to 1.18 +/- 0.02). Group 2 was studied during carbonic anhydrase inhibition (CAI) produced by benzolamide before and during superimposed AVE (20% body wr). Both (TF/P)In (from 1.91 +/- 0.10 to 1.41 +/- 0.08) and (TF/UF)Cl (from 1.07 +/- 0.02 to 1.01 +/- 0.01) decreased. Group 3 was studied during maintained AVE (15% body wt) as a control for group 4, in which CAI was superimposed on maintained AVE. In group 3, (TF/P)In and (TF/UF)Cl did not change, but in group 4 CAI was associated with a decrease in (TF/P)In (from 1.55 +/- 0.05 to 1.21 +/- 0.05) and in (TF/UF)Cl (from 1.16 +/- 0.01 to 1.04 +/- 0.07). These data suggest that in the superficial proximal convoluted tubule of the rat, AVE-induced alterations in transepithelial chloride gradient are dependent on a mechanism(s) other than changes in carbonic anhydrase-mediated bicarbonate reabsorption.

Animals↗