Nitric oxide regulates HCO3- and Na+ transport by a cGMP-mediated mechanism in the kidney proximal tubule

The effects of nitric oxide (NO) on blood pressure and renal hemodynamics are well established, but those of NO on renal tubule HCO3- and Na+ transport are not fully understood. In this study, we combined renal clearance and in situ microperfusion techniques to investigate the effects of NO on the renal excretion of Na (FE(Na%)) and the rates of renal tubule absorption of fluid (J(v)) and bicarbonate (J(HCO3)) in the rat kidney. Administration of the nitric oxide synthase inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME, 6 mg/kg iv bolus) did not change mean blood pressure and glomerular filtration rate significantly. However, L-NAME significantly increased urine flow rate and FE(Na%), and these effects were maintained over a 60-min period. Addition of L-NAME markedly decreased both J(v) and J(HCO3) in the proximal tubule. In contrast, addition of 1 mu M sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP) significantly increased both J(v) and J(HCO3). Similar stimulation was also observed when 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 1 mu M) was added to the luminal perfusate. The stimulatory effects of SNP and 8-BrcGMP on J(v) and J(HCO3) were not additive. The increments in J(v) and J(HCO3) due to SNP were abolished by the Na+/H+ exchange blocker ethylisopropylamiloride and the guanylate cyclase inhibitor methylene blue. These results indicate that NO stimulates proximal tubule Na+ and HCO3- transport through a cGMP-linked pathway in the kidney proximal tubule.