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 microM 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 microM) 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.
Wang
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Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
D000042:Absorption / Q000187:drug effects; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism; D006152:Cyclic GMP / Q000494:pharmacology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D012964:Sodium / Q000378:metabolism*
D001639:Bicarbonates; D004791:Enzyme Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D012964:Sodium; D010396:Penicillamine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester