Delivery dependence of early proximal bicarbonate reabsorption in the rat in respiratory acidosis and alkalosis.

Abstract

In the intact rat kidney, bicarbonate reabsorption in the early proximal tubule (EP) is strongly dependent on delivery. Independent ofdelivery, metabolic acidosis stimulates EP bicarbonate reabsorption. In this study, we investigated whether systemic pH changes induced by acute or chronic respiratory acidbase disorders also affect EP HCO3 reabsorption, independent of delivery (FLHCO3, filtered load of bicarbonate). Hypercapnia was induced in rats acutely (1-3 h) and chronically (4-5 d) by increasing inspired Pco2. Hypocapnia was induced acutely (1-3 h) by mechanical hyperventilation, and chronically (4-5 d) using hypoxemia to stimulate ventilation. When compared with normocapneic rats with similar FLHco3, no stimulation of EP or overall proximal HCO3 reabsorption was found with either acute hypercapnia (Pac = 74 mmHg, pH = 7.23) or chronic hypercapnia (Pa<> = 84 mmHg, pH = 7.31). Acute hypocapnia (Pac, = 29 mmHg, pH = 7.56) did not suppress EP or overall HC03 reabsorption. Chronic hypocapnia (Pa2 = 26 mmHg, pH = 7.54) reduced proximal HCO3 reabsorption, but this effect was reversed when FLHCo3 was increased to levels comparable to euvolemic normocapneic rats. Thus, when delivery is accounted for, we could find no additional stimulation of proximal bicarbonate reabsorption in respiratory acidosis and, except at low delivery rates, no reduction in bicarbonate reabsorption in respiratory alkalosis. (J. Clin. Invest. 1991. 87:631-638.)

Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis

“…b OKP cells transfected with Nhe3 promoter sequences spanning −2,094/+55 or −152/ +55 were subjected to respiratory acidosis. Promoter activity is given by the ratio of Nhe3 promoter signal (Firefly luciferase) by the transfection control (Renilla luciferase); *p<0.05 and, if the filtration rate is not affected, to a higher filtered bicarbonate load [27,38]. It has been shown that the metabolic compensation for respiratory acidosis is achieved by the kidneys [25,37], which increase the secretion of acid into the urine and the transport of HCO 3 − into the blood, thereby elevating plasma pH.…”

“…However, there are discrepant findings regarding the functional modulation of NHE3 in response to high pCO 2 . Santella et al observed that, in rats subjected to chronic respiratory acidosis, there was no increase in early proximal tubule HCO 3 − reabsorption when HCO 3 − delivered to the nephron was similar to that observed in normocapneic rats, suggesting that the higher HCO 3 − reabsorption rate is merely a consequence of the increased HCO 3 − available to proximal tubules in the setting of respiratory acidosis [38]. Zeidel et al also found no increase in NHE activity in vesicles prepared from rabbits exposed to chronic hypercapnia, despite the profound respiratory acidosis observed in those animals [47].…”

Disorders of Acid-Base Balance: New Perspectives

“…The decreased glomerular filtration rate due to hypoxemia and hypercarbia and the increased bicarbonate reabsorption caused by high pCO 2 causes extracellular volume expansion (as in cor pulmonale). The elevated plasma bicarbonate level (and low chloride) reaches a new steady state much like the steady state of mineralocorticoid excess: newly elevated plasma bicarbonate increases the filtered load of bicarbonate enough so that, even under the influence of hypercapnia to increase proximal tubular reabsorption of sodium bicarbonate, sufficient delivery of bicarbonate to the distal nephron allows for no further generation of new bicarbonate [26] . And since bicarbonate generation depends on ammonia present in the collecting duct lumen, the limited maximal capacity for ammonia synthesis is important.…”

Cross-Talk between Two Organs: How the Kidney Responds to Disruption of Acid-Base Balance by the Lung

“…Micropuncture and microperfusion studies have documented suppressed proximal and distal acidification during acute hypocapnia, including decreased proximal bicarbonate reabsorption, and depressed formation and delivery of ammonium and titratable acid [25, 26, 27]; reduced proximal bicarbonate reabsorption was also demonstrated by micropuncture in chronic hypocapnia [28]but distal acidification has not been examined with these techniques in chronic hypocapnia. A reduction in systemic PCO 2 also leads to a disproportional reduction in renal cortical PCO 2 and augmentation of proximal chloride reabsorption.…”