Proximal tubular bicarbonate reabsorption and PCO2 in chronic metabolic alkalosis in the rat.

Abstract

A B S T R A C T Studies were undertaken to define the pattern of proximal tubular bicarbonate reabsorption and its relation to tubular and capillary Pco2 in rats with chronic metabolic alkalosis (CMA). CMA was induced by administering furosemide to rats ingesting a low electrolyte diet supplemented with NaHCO3 and KHC03. Proximal tubular bicarbonate reabsorption and Pco2 were measured in CMA rats either 4-7 or 11-14 d after furosemide injection, in order to study a wide range of filtered bicarbonate loads. A group of nine age-matched control animals, fed the same diet but not given furosemide, was studied for comparison. In a third group of controls, the filtered load of bicarbonate was varied over the same range as in the CMA rats by plasma infusion and aortic constriction. The CMA rats had significant alkalemia and hypokalemia (4-7 d: pH 7.58, HCO3 38.3 meq/liter, K+ 2.1 meq/liter; 11-14 d: pH 7.54, HCO3 38.1 meq/liter, K+ 2.5 meq/liter). Nonetheless, proximal bicarbonate reabsorption was not significantly different from that seen in control rats at any given load of filtered bicarbonate (from 250 to 1,300 pmol/min). In both control and CMA rats, 83-85% of the filtered bicarbonate was reabsorbed by the end of the accessible proximal tubule. These observations indicate that proximal bicarbonate reabsorption is determined primarily by the filtered load in chronic metabolic alkalosis. When single nephron glomerular filtration rate (SNGFR) is reduced by volume depletion in the early postfurosemide period, the filtered load and the rate of proximal bicarbonate reabsorption remain at or below control lev-

Effect of acute changes in glomerular filtration rate on Na+/H+ exchange in rat renal cortex.

“…The proximal convoluted tubule of the rat nephron normally reabsorbs 80% of the filtered load of bicarbonate (FLHC,),' and the reabsorptive rate in this segment of the nephron is highly dependent on bicarbonate delivery (1,2). As bicarbonate is reabsorbed, luminal pH and bicarbonate concentration fall along the length of the nephron (1, [3][4][5][6].…”

Load dependence of proximal tubular fluid and bicarbonate reabsorption in the remnant kidney of the Munich-Wistar rat.

“…The rats were prepared for micropuncture as described previously (19). They were maintained on a small animal ventilator with added 02 to maintain 02 tension (Po2) at -100 mmHg (mean Po2 = 100±4 mmHg in controls, 97±3 mmHg in the normal protein remnant kidney rats and 114±5 mmHg in the low protein remnant kidney rats).…”

“…At the end of surgery, 0.4 ml of Ringer's solution containing either 25 gCi (controls) or 12 gCi (remnant kidney rats) of [14C]inulin was given as a bolus and was followed by an infusion at 0.84 ml/h to deliver 52 PCi/h in control rats and 26 MCi/h in the remnant kidney rats. After a 45-min equilibration period, timed micropuncture collections were obtained from Bowman's space and from early, mid-, and late proximal tubular sites as described previously (19,20). The puncture sites were marked with a nigrosine-containing saline solution.…”

“…Tubular fluid, Bowman's space, and urine total CO2 concentrations were measured by microcalorimetry (22). The total CO2 concentration measured in tubular fluid was assumed to equal the tubular fluid bicarbonate concentration, because we have shown previously that the Pco2 in nanoliter volume tubular fluid samples falls to zero before microcalorimetry can be performed (19). SNGFR and proximal reabsorption rates were calculated using standard formulas.…”

“…Early proximal tubule bicarbonate reabsorptive capacity was found to be much greater than 200 pmol/mm * min when the filtered load of bicarbonate was increased acutely by increasing SNGFR (1 1). Primarily because of the high reabsorptive capacity of the early proximal tubule (1 1), total proximal bicarbonate reabsorption increases as a function of filtered load in the normal rat when SNGFR is increased acutely (10,11,19). Based on these observations, proximal bicarbonate reabsorption might be expected to increase in the remnant kidney independent of any anatomic change.…”