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PubMed1991

Augmented bidirectional HCO3 transport by rat distal tubules in chronic alkalosis.

Free-flow micropuncture studies show both augmented net HCO3 reabsorption in the distal tubule of rats with chronic metabolic alkalosis and higher HCO3 delivery to this nephron segment. The present studies in rats used in vivo microperfusion of surface distal tubules to investigate whether the augmented net reabsorption 1) was due to decreased HCO3 secretion and/or to increased proton secretion or 2) depended on the higher HCO3 delivery to the distal tubule. Artificial perfusates were designed to simulate in situ deliveries of HCO3 to the distal tubules of both alkalotic and control animals and to represent extremes of in situ Cl deliveries. Rather than being decreased, both measured and calculated HCO3 secretion were higher in the alkalotic animals for each perfusate used. Similarly, calculated proton secretion (difference between net HCO3 reabsorption and calculated HCO3 secretion) was higher for the alkalotic animals using each HCO3-containing perfusate. Augmented net HCO3 reabsorption by alkalotic animals was more clearly demonstrated using higher HCO3 deliveries and Cl-free perfusates. These studies demonstrate that both the reabsorptive and secretory components of net HCO3 transport are increased in the distal tubule of animals with chronic metabolic alkalosis.

Absorption↗
PubMed1991

Absence of a regulatory role of angiotensin II in acute chloride-depletion alkalosis in rats.

Chloride-depletion alkalosis (CDA) has been characterized by hypereninemia. To determine whether angiotensin II (ANG II) has an important role in its maintenance or correction, anesthetized alkalotic rats, chloride depleted by peritoneal dialysis, were infused with 5% dextrose and saralasin (1 microgram.kg-1.min-1) (SAR) or vehicle (SAR-C), 5% dextrose and pretreatment with enalapril (1-1.5 mg/kg) (ENP) or vehicle (ENP-C), or 80 mM Cl solution with ANG II (20 micrograms/min) (ANG) or vehicle (ANG-C). Rats infused with 5% dextrose showed no differences in the magnitude of the alkalosis, inulin clearance, or urinary total CO2 excretion; both SAR and ENP were associated with decreased blood pressure. In SAR, tCO2 delivery out of late proximal convoluted tubule did not differ from that in SAR-C. Rats infused with 80 mM Cl corrected CDA similarly (delta plasma [Cl] - ANG-C + 6 +/- 1, ANG + 5 +/- 1 mM; P = not significant). These data suggest that, although ANG II can importantly influence vascular tone and early proximal tubule bicarbonate reabsorption, it does not have an important role in the renal maintenance or correction of acute CDA.

Alkalosis↗
PubMed1992

Effect of metabolic acidosis and alkalosis on NEM-sensitive ATPase in rat nephron segments.

An N-ethylmaleimide (NEM)-sensitive adenosinetriphosphatase (ATPase) displaying the kinetic and pharmacological properties of an electrogenic proton pump has been described in the different segments of rat nephron, where it mediates part of the active tubular proton secretion. This study was therefore designed to evaluate whether changes in urinary acidification observed during metabolic acidosis or alkalosis were associated with alterations of the activity of tubular NEM-sensitive ATPase, and if so, to localize the nephron segments responsible for these changes. Within 1 wk after the onset of ammonium chloride treatment, rats developed a metabolic acidosis, and NEM-sensitive ATPase activity was markedly increased in the medullary thick ascending limb of Henle's loop and outer medullary collecting tubule, and slightly increased in the cortical collecting tubule. Conversely, treatment with sodium bicarbonate induced a metabolic alkalosis that was accompanied by decreased NEM-sensitive ATPase activity in medullary thick ascending limb and outer medullary collecting tubule. NEM-sensitive ATPase activity was not altered in any other nephron segment tested in alkalotic and acidotic rats, i.e., the proximal tubule and the cortical thick ascending limb of Henle's loop. Changes qualitatively similar were observed as soon as 3 h after the onset of NaHCO3 or NH4Cl-loading. In the medullary collecting tubule, alterations of NEM-sensitive ATPase activity are in part due to hyperaldosteronism observed in both acidotic and alkalotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1994

Effect of respiratory acidosis and respiratory alkalosis on renal transport enzymes.

We studied the effect of respiratory acidosis and respiratory alkalosis on acid-base composition and on microdissected renal adenosinetriphosphatase (ATPase) enzymes. Rats were subjected to hypercapnia or hypocapnia of 6, 24, and 72 h duration. After 6 h of hypercapnia, collecting tubule (CT) ATPases were not changed. At 24 h, plasma bicarbonate was 35 +/- 1 meq/l (P < 0.01) and CT H-ATPase and H-K-ATPase activities were 90% greater than controls (P < 0.01). By 72 h, plasma bicarbonate was 37 +/- 1 meq/l (P < 0.005 vs. control) and CT enzyme activity had increased even more, averaging approximately 130% of control (P < 0.05). Significant increases in enzyme activities were also observed in the proximal convoluted tubule and medullary thick ascending limb. Plasma aldosterone was three to four times that of control at all three time periods. In hormone-replete adrenalectomized rats, acid-base parameters and ATPase activities were the same as those seen in adrenal intact animals. After 6 h of hypocapnia, plasma bicarbonate was not significantly changed, but H-ATPase and Na-K-ATPase activities were decreased by 35% along the entire nephron (P < 0.05). H-K-ATPase activity in CT also decreased by 35%. At 24 h, plasma bicarbonate was 20.5 +/- 0.5 meq/l (P < 0.05 vs. control) and CT H-ATPase and H-K-ATPase activities were 60% less than control (P < 0.01). By 72 h, plasma bicarbonate was 18.5 +/- 0.5 meq/l (P < 0.05); however, only CT H-ATPase activity continued to fall, averaging 75% less than control (P < 0.005). Hypocapnia had no effect on plasma aldosterone or potassium. These results demonstrate that chronic, but not acute, respiratory acidosis stimulates activity of both renal proton ATPases. By contrast, both acute and chronic respiratory alkalosis decrease the two renal proton pumps. The stimulatory effect of hypercapnia and the inhibitory effect of hypocapnia on the renal ATPases appear to be potassium and aldosterone independent. Although the precise mechanisms for these results are not known, a direct effect of PCO2, pH, or changes in bicarbonate delivery may be involved.

Acidosis, Respiratory↗
PubMed1995

Neutral phosphate administration generates and maintains renal metabolic alkalosis and hyperparathyroidism.

We examined the effects of chronic intravenous neutral phosphate administration on systemic acid-base equilibrium and parathyroid function in six normal, NaCl-replete male human subjects under metabolic balance conditions. The subjects received 4.35 mmol of neutral sodium phosphate.kg body wt-1.day-1 intravenously and continuously for 7 days and the same amount of sodium as NaCl during control and recovery. Blood pH increased from 7.388 to 7.411 (P < 0.001) and plasma bicarbonate from 23.5 to 26.0 mmol/l (P < 0.001). Urinary pH increased from 6.58 to 6.79 (P < 0.001). Net acid excretion increased from 59 to 100 mmol/24 h (P < 0.001). Plasma ionized calcium concentration decreased and plasma phosphate concentration increased transiently. Serum intact parathyroid hormone increased from 24 to 62 pg/ml (P < 0.001). Chronic phosphate administration also resulted in a significant increase in renal phosphate clearance (35 to 229 ml/min) and decrease in the fractional excretion of calcium (1.8 to 0.9%). Thus chronic intravenous phosphate administration generates and maintains renal metabolic alkalosis in salt-replete humans and induces hyperparathyroidism. The severity of metabolic alkalosis is mitigated by an apparent increase in effective endogenous acid production as evidenced by the significant increase in steady-state net acid excretion.

Acid-Base Equilibrium↗
PubMed1996

The molecular basis of inherited hypokalemic alkalosis: Bartter's and Gitelman's syndromes.

Hypokalemic alkalosis with low blood pressure can be caused by a number of medications or alternatively as an autosomal recessive genetic trait. Molecular genetic approaches to this problem have recently demonstrated that mutations in genes encoding the thiazide-sensitive Na-Cl cotransporter or the bumetanide-sensitive Na-K-2Cl cotransporter produce two distinctive clinical and physiological pictures featuring hypokalemic alkalosis. Mutations in the latter cause a phenotypic picture called Bartter's syndrome that includes marked hypercalciuria and neonatal presentation with marked intravascular volume depletion. Mutations in the former cotransporter result in Gitelman's syndrome, which includes hypocalciuria, hypomagnesemia, and typically older clinical presentation with predominant muscular signs and symptoms. These findings establish the molecular basis of these disorders and indicate that the diverse abnormalities seen in affected patients derive from primary defects in these mediators of cotransport function. Moreover, these findings have implications for normal mechanisms of renal electrolyte homeostasis and for potential phenotypic effects in the more common heterozygous carriers of these mutations.

Alkalosis↗
PubMed1981

Changes in brain surface pH during acute isocapnic metabolic acidosis and alkalosis.

It has been thought that the blood-brain barrier is relatively impermeable to changes in arterial blood H+ and OH- concentrations. We have measured the brain surface pH during 30 min of isocapnic metabolic acidosis or alkalosis induced by intravenous infusion of 0.2 N HCl or NaOH in anesthetized dogs. The mean brain surface pH fell significantly by 0.06 and rose by 0.04 pH units during HCl or NaOH infusion, respectively. Respective changes were also observed in the calculated cerebral interstitial fluid [HCO-3]. There were no significant changes in cisternal cerebrospinal fluid acid-base variables. It is concluded that changes in arterial blood H+ and OH- concentrations are reflected in brain surface pH relatively quickly. Such changes may contribute to acute respiratory adaptations in metabolic acidosis and alkalosis.

Acidosis↗
PubMed1986

Hyperventilation, alkalosis, prostaglandins, and pulmonary circulation of the newborn.

This study was designed to determine whether the effects of hyperventilation on the pulmonary circulation of the newborn lamb were 1) due to mechanical factors or to respiratory alkalosis; and 2) mediated by prostaglandins. Six control lambs were studied during normal ventilation and during hyperventilation with, and without, decreased carbon dioxide (CO2). Five lambs were given indomethacin and studied similarly. In control lambs, hyperventilation with decreased CO2 decreased pulmonary arterial pressure from 26 +/- 2.2 to 18 +/- 1.0 (SE) Torr (P less than or equal to 0.005) and pulmonary vascular resistance from 0.099 +/- 0.035 to 0.070 +/- 0.011 Torr X kg-1 X min-1 (P less than or equal to 0.015). Hyperventilation with normal CO2 did not affect the pulmonary circulation. Hyperventilation with decreased CO2 increased pulmonary arterial concentrations of 6-ketoprostaglandin F1 alpha, a major metabolite of prostacyclin, in control lambs but not in the indomethacin-treated lambs. However, it affected the pulmonary circulation of the control- and indomethacin-treated lambs similarly. In conclusion, hyperventilation affected the pulmonary circulation by respiratory alkalosis not by mechanical factors and prostaglandins did not mediate its effects.

6-Ketoprostaglandin F1 alpha↗
PubMed2004

Preexercise metabolic alkalosis induced via bicarbonate ingestion accelerates Vo2 kinetics at the onset of a high-power-output exercise in humans.

The present study investigated the effect of preexercise metabolic alkalosis on the primary component of oxygen uptake (Vo(2)) kinetics, characterized by tau(1). Seven healthy physically active nonsmoking men, aged 22.4 +/- 1.8 (mean +/- SD) yr, maximum Vo(2) (Vo(2 max)) 50.4 +/- 4 ml.min(-1).kg(-1), performed two bouts of cycling, corresponding to 40 and 87% of Vo(2 max), lasting 6 min each, separated by a 20-min pause, once as a control study and a few days later at approximately 90 min after ingestion of 3 mmol/kg body wt of NaHCO(3). Blood samples for measurements of bicarbonate concentration and hydrogen ion concentration were taken from antecubital vein via catheter. Pulmonary Vo(2) was measured continuously breath by breath. The values of tau(1) were calculated by using six various approaches published in the literature. Preexercise level of bicarbonate concentration after ingestion of NaHCO(3) was significantly elevated (P < 0.01) compared with the control study (28.96 +/- 2.11 vs. 24.84 +/- 1.18 mmol/l; P < 0.01), and [H(+)] was significantly (P < 0.01) reduced (42.79 +/- 3.38 nmol/l vs. 46.44 +/- 3.51 nmol/l). This shift (P < 0.01) was also present during both bouts of exercise. During cycling at 40% of Vo(2 max), no significant effect of the preexercise alkalosis on the magnitude of tau(1) was found. However, during cycling at 87% of Vo(2 max), the tau(1) calculated by all six approaches was significantly (P < 0.05) reduced, compared with the control study. The tau(1) calculated as in Borrani et al. (Borrani F, Candau R, Millet GY, Perrey S, Fuchsloscher J, and Rouillon JD. J Appl Physiol 90: 2212-2220, 2001) was reduced on average by 7.9 +/- 2.6 s, which was significantly different from zero with both the Student's t-test (P = 0.011) and the Wilcoxon's signed-ranks test (P = 0.014).

Administration, Oral↗
PubMed1987

Effect of acidosis and alkalosis on divalent ion transport across the proximal straight tubule of the rabbit.

In vitro microperfusion experiments were performed on the cortical proximal straight tubule of the rabbit to examine the effect of acid base disturbances on calcium and magnesium transport by this segment of the nephron. During acidosis (pH 7.22 +/- 0.01) net calcium reabsorption was reduced, whereas during alkalosis (pH 7.82 +/- 0.02) net calcium reabsorption was increased. Our flux experiments with 45Ca indicate that the efflux of Ca from the lumen to the bath remained the same during acidosis; however, the back-flux (bath to lumen) of calcium increased. On the other hand, during alkalosis the efflux of calcium rose and the influx of calcium remained unchanged. These changes in fluxes during acid-base disturbances can be accounted for mainly by changes in ionized calcium as a result of pH changes. We failed to observe any effect of acid-base changes on net magnesium transport by the superficial proximal straight tubule.

Acidosis↗
PubMed1990

Chronic cerebral intracellular alkalosis following forebrain ischemic insult in rats.

We measured cerebral intracellular pH using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy during 1 week after forebrain ischemia or sham operation in eight and seven rats, respectively. Mean maximum pH was significantly higher (p less than 0.003) in the ischemic group than in the sham-operated group (7.34 +/- 0.03 and 7.19 +/- 0.02, respectively). The difference between mean maximum pH and baseline pH (7.08 +/- 0.01 in each group) was significantly greater (p less than 0.02) in the ischemic group than in the sham-operated group. In the ischemic group, alkalosis occurred primarily after 48-72 hours of recirculation. We speculate that brain tissue alkalosis occurring chronically after ischemia is associated with delayed ischemic neuronal death.

Alkalosis↗
PubMed1990

Effects of metabolic alkalosis on pulmonary gas exchange.

In order to investigate whether the changes in PaO2 reported during acid-base disturbances are due to modifications of ventilation/perfusion relationships or only to extrapulmonary factors, we studied the hemodynamics and blood gases of eight critically ill patients maintained in constant mechanical ventilation, before and after selective correction of metabolic alkalosis by infusion of 1 N hydrochloric acid (HCl). HCl infusion decreased arterial pH from 7.55 to 7.40 (p less than 0.001) and increased PaO2 from 76 to 98 mm Hg (p less than 0.05) at the end of the study. Cardiac output and oxygen consumption did not change. In patients with initial venous admixture (QS/QT) less than 20% (n = 4), QS/QT did not change, and hemoglobin saturation decreased, whereas PaO2 increased from 87 to 96 mm Hg (p less than 0.10), indicating a shift in the oxyhemoglobin dissociation curve caused by the Bohr effect. In patients with QS/QT greater than 20% (n = 4), QS/QT decreased from 27 to 22% (p less than 0.05), hemoglobin saturation increased from 93 to 96% (p less than 0.05), and PaO2 increased from 65 to 100 mm Hg (p less than 0.05), which reflects an improvement in ventilation/perfusion relationships, probably because of enhanced hypoxic pulmonary vasoconstriction. These data indicate that metabolic alkalosis deteriorates pulmonary ventilation/perfusion relationships in patients with marked respiratory failure (QS/QT greater than 20%), and that reversing this effect with HCl infusion can improve PaO2 significantly.

Adult↗
PubMed1971

Changes in bone sodium and carbonate in metabolic acidosis and alkalosis in the dog.

Metabolic acidosis and alkalosis were produced in adult dogs over 5- to 10-day periods. Midtibial cortical bone was analyzed for calcium, sodium, phosphorus, and carbonate. In acidosis bone CO(3)/Ca decreased 9.5% and bone Na/Ca decreased 6.3%. In alkalosis bone CO(3)/Ca increased 3.1% and bone Na/Ca increased 3.0%. Previous attempts to account for changes in net acid balance by summation of extra- and intracellular acid-base changes have uniformly resulted in about 40-60% of acid gained or lost being "unaccounted for." If it is assumed that changes in tibial cortex reflect changes in the entire skeletal system, changes in bone CO(3) (=) are sufficiently large to account for the "unaccounted for" acid change without postulating changes in cellular metabolic acid production.

Acidosis↗
PubMed1971

Regulatory mechanisms of hemoglobin oxygen affinity in acidosis and alkalosis.

The recent reports of the effect of 2,3-diphosphoglycerate (2,3-DPG) on hemoglobin affinity for oxygen suggested that this substance may play a role in man's adaptation to acidosis and alkalosis.A study of the effect of induced acidosis and alkalosis on the oxyhemoglobin dissociation curve of normal man was therefore carried out, and the mechanisms involved in the physiological regulation of hemoglobin oxygen affinity examined.In acute changes of plasma pH there was no alteration in red cell 2,3-DPG content. However, there were changes in hemoglobin oxygen affinity and these correlated with changes in mean corpuscular hemoglobin concentration (MCHC). With maintained acidosis and alkalosis, red cell 2,3-DPG content was altered and correlated with the changes in hemoglobin oxygen affinity. Both of these mechanisms shift the hemoglobin oxygen dissociation curve opposite to the direct pH (Bohr) effect, and providing the rate of pH change is neither too rapid nor too large, they counteract the direct pH effect and the in vivo hemoglobin oxygen affinity remains unchanged. It is also shown that approximately 35% of the change in hemoglobin oxygen affinity resulting from an alteration in red cell 2,3-DPG, is explained by effect of 2,3-DPG on the red cell pH.

Acidosis↗
PubMed1972

Glucose-induced alkalosis in fasting subjects. Relationship to renal bicarbonate reabsorption during fasting and refeeding.

This study documents the development of alkalosis in patients returning to caloric intake after a period of starvation and investigates the mechanisms responsible for this metabolic alteration. We studied the acid-base status, bicarbonate reabsorption, acid excretion, and sodium metabolism during fasting and glucose refeeding in 19 patients receiving sodium supplements. Metabolic alkalosis developed promptly in all of the subjects who terminated an 18 day fast with 300 g of glucose daily for 4 days. Tubular maximum reabsorptive capacity for bicarbonate and renal bicarbonate threshold determinations were performed at varying intervals in six and seven subjects, respectively, who had fasted for 3-18 days. The results demonstrated that bicarbonate reabsorptive capacity was normal or low during early fasting, markedly elevated during the 2nd wk; and moderately elevated during the 3rd wk of fasting. Glucose administration at all stages of fasting caused a further increase in bicarbonate threshold. Sodium balance during fasting with sodium supplements was found to follow a triphasic pattern, with the occurrence of a natriuresis during the 1st wk followed by a period of sodium retention after which neutral daily sodium balance was reestablished. Correlation of bicarbonate reabsorption with sodium homeostasis indicated a slight decrease in renal bicarbonate threshold during the natriuretic phase, a marked increase in bicarbonate reabsorption during the period of sodium retention, and a continued moderate elevation of threshold after sodium balance was reestablished. This relationship was interpreted to indicate that changes in bicarbonate reabsorption during fasting and refeeding may be secondary to alterations in the renal reabsorption of sodium.

Absorption↗
PubMed1972

Pathogenesis of congenital alkalosis with diarrhea. Implications for the physiology of normal ileal electrolyte absorption and secretion.

Using a triple-lumen constant perfusion system, we have studied ileal electrolyte transport in a patient with congenital alkalosis with diarrhea and made the following observations. First, chloride cannot be transported against electrochemical gradients, but can be readily absorbed or secreted down electrochemical gradients. Second, chloride secretion down an electrochemical gradient can be increased by raising lumen bicarbonate concentration. Third, sodium absorption does occur against electrochemical gradients and is associated with hydrogen ion secretion. Fourth, electrical potential difference (PD) between lumen and blood is near zero when lumen sodium concentration is 140 mEq/liter. Fifth, a normal sodium diffusion potential is present. Sixth, potassium is transported passively in response to electrochemical gradients. The ileal electrolyte transport disorder of congenital alkalosis with diarrhea can be simulated exactly in normal subjects perfused with a solution in which chloride is replaced with poorly absorbable sulfate and phosphate. These results can be explained by postulating a single defect in the double ion exchange model (sodium-hydrogen, chloride-bicarbonate) previously proposed for normal ileal transport: i.e., normal sodium-hydrogen exchange, but a chloride-bicarbonate exchange that is incapable of transporting chloride against an electrochemical gradient, yet continues to transport anions passively. In contrast, the results appear incompatible with the concept of ileal electrogenic sodium transport.

Adult↗
PubMed1984

Volume-independent reductions in glomerular filtration rate in acute chloride-depletion alkalosis in the rat. Evidence for mediation by tubuloglomerular feedback.

We have recently described reduced superficial nephron glomerular filtration rate (SNGFR) in chloride-depletion alkalosis (CDA) without volume depletion. To elucidate the mechanism of this phenomenon, we studied three degrees of increasing severity of CDA (groups CDA-1, 2, and 3) produced by one or two peritoneal dialyses against 0.15 M NaHCO3 and electrolyte infusions of different Cl and HCO3 content in Sprague-Dawley rats; control rats (CON) were dialyzed against and infused with Ringers-HCO3. Extracellular fluid (ECF) volume was assessed by blood pressure, hematocrit, plasma protein concentration, and 125I-albumin space; none of these variables differed among the four groups. Micropuncture of the latest proximal and earliest distal convolutions was carried out. As CDA intensified from CON to CDA-3 (plasma tCO2 25 +/- 1 to 43 +/- 1 meq/L; P less than 0.01), distally determined SNGFR declined progressively (40.9 +/- 1.7 to 28.3 +/- 1.8 nl/min; P less than 0.01), while in early distal tubule fluid, flow rate (8.6 +/- 0.7 to 3.4 +/- 0.6 nl/min) and Cl concentration (36 +/- 2 to 19 +/- 3 meq/L) decreased and osmolality (110 +/- 5 to 208 +/- 12 mosmol/kg) increased (P less than 0.01), and, in the loop segment, Cl reabsorption decreased progressively (2,009 +/- 112 to 765 +/- 128 peq/min; P less than 0.01). In early distal tubule fluid, Cl concentration correlated positively and osmolality negatively with distally determined SNGFR (P less than 0.05). Proximally determined SNGFRs did not differ among the four groups. Proximal tubule stop-flow pressure responses to increasing rates of orthograde perfusion of the loop segment from 0 to 40 nl/min did not differ between groups CON and CDA-2. We interpret these data to show that reductions in SNGFR in CDA in the rat can occur by tubuloglomerular feedback (TGF) in the absence of differences in ECF volume or of alterations in TGF sensitivity during metabolic alkalosis. Of the proposed signals for TGF sensed by the macula densa, distal tubule fluid osmolality or some related variable is the signal most compatible with our data.

Alkalosis↗
PubMed1986

Load dependence of proximal tubular bicarbonate reabsorption in chronic metabolic alkalosis in the rat.

Studies were undertaken in Munich-Wistar rats to determine whether maintenance of chronic metabolic alkalosis (CMA) is associated with an increase in proximal HCO3- reabsorption, or whether a reduction in glomerular filtration rate (GFR) is required to sustain the elevated plasma HCO3- concentration. Superficial single nephron glomerular filtration rate (SNGFR), and absolute proximal HCO-3 (APRHCO3) and water (APRH2O) reabsorption were measured 20 +/- 3 d after the induction of CMA in eight rats and the results compared with seven age-matched control animals. Plasma [HCO3-] was 39.1 +/- 1.8 mM in CMA rats compared with 26.0 +/- 0.4 mM in controls (P less than 0.001). In the CMA rats, SNGFR was 44.8 +/- 1.1 vs. 38.2 +/- 2.1 nl/min in controls (P less than 0.025). As a result, the single nephron filtered load of HCO3- (FLHCO3) increased from 1,147 +/- 61 pmol/min in control to 2,040 +/- 108 pmol/min in CMA (P less than 0.001). APRHCO3 increased by greater than 65%, from 970 +/- 65 pmol/min in control to 1,624 +/- 86 pmol/min in CMA (P less than 0.001). APRH2O increased from 18.4 +/- 1.6 nl/min in control to 24.0 +/- 0.8 nl/min in CMA (P less than 0.005). Tubular hypertrophy resulted in an increase in the length of the proximal convoluted tubule from 5.6 +/- 0.2 to 6.5 +/- 0.2 mm (P less than 0.005). The pattern of HCO3- reabsorption along the length of the proximal convoluted tubule in CMA was indistinguishable from that found in normal rats in which FLHCO3 was varied acutely by altering SNGFR. The increase in tubular length accounted for only 30% of the increase in APRH2O and 15% of the increase in APRHCO3. We conclude that a sustained reduction in GFR is not required for maintenance of CMA in the rat. If GFR is chronically restored to normal levels, the alkalosis is maintained by an increase in APRHCO3. The increase in reabsorption is accounted for by tubular hypertrophy, a chronic adaptive response, and a load-dependent response that is indistinguishable from that seen in normal rats when FLHCO3 is increased acutely by increasing SNGFR.

Alkalosis↗