Glucocorticoids enhance the expression of the basolateral Na+: HCO3- cotransporter in renal proximal tubules

Background, Studies have shown that glucocorticoids enhance HCO3- reabsorpt ion in proximal tubules. Functional and molecular studies indicate that HCO 3- reabsorption in proximal tubules is mediated via luminal H+-ATPase and N a+/H+ exchanger (NHE-3), and basolateral Na+:HCO3- co-transporter (NBC) act ing in series. The purpose of these experiments was to examine the effect o f adrenal steroids on NBC-1 and NHE-3 expression and activity in rat renal proximal tubules. Methods. Rats were injected subcutaneously with dexamethasone (100 mu/day) or deoxycorticosterone acetate (30 mg/kg), potent glucocorticoid, or minera locorticoid analogues, respectively. Animals were sacrificed after two or f our days, and NBC-1 and NHE-3 mRNA expression and activities were measured in cortex and proximal tubules. Results. Northern hybridizations indicated that cortical NBC-1 mRNA express ion increased by approximately 92% in rats treated with dexamethasone for f our days (N = 6, P < 0.03) but not two days. NHE-3 mRNA expression remained unchanged. NBC and NHE-3 activities were measured as the Na-dependent pH(i ) recovery from an acid load in the presence or absence of HCO3-, respectiv ely, and appropriate inhibitors in proximal tubule suspensions loaded with BCECF. NBC activity increased by approximately 80% in rats treated with dex amethasone for four days (P < 0.01, N = 5) but not two days. NHE-3 activity increased by 34 and 42% in rats treated with dexamethasone for two and fou r days, respectively (P < 0.05 and P < 0.02 for each group vs, control). Tr eatment with deoxycorticosterone acetate did not alter NBC-1 expression. Conclusion. Glucocorticoids at pharmacologic concentrations enhance the mRN A expression and functional activity of renal proximal tubule NBC-1. Enhanc ed NBC and NHE-3 activities could result in increased HCO3- reabsorption in proximal tubule and could contribute to the maintenance of metabolic alkal osis in pathophysiologic states associated with increased glucocorticoid pr oduction.