Nitric oxide inhibits sodium reabsorption in the isolated perfused cortical collecting duct.

Indirect evidence suggests that nitric oxide inhibits sodium reabsorption by the collecting duct; however, direct evidence is lacking. It was hypothesized that endothelium-derived nitric oxide inhibits sodium flux in the cortical collecting duct by blocking amiloride-sensitive sodium channels. Tubules were obtained from Sprague-Dawley rats pretreated with deoxycorticosterone acetate (5 mg/rat i.m.) 5 to 9 days before the experiment. Nitric oxide was added to the system by either the addition of endothelial cells and the induction of the release of nitric oxide via acetylcholine (10(-7) M) or by the addition of nitric oxide donors. Acetylcholine-induced nitric oxide release from endothelial cells decreased lumen-to-bath sodium flux by 24 +/- 7% (N = 3; P < 0.05). The addition of the nitric oxide donor, spermine NONOate (10(-5) M), decreased net sodium flux 68% from 10.1 +/- 2.0 to 3.6 +/- 2 pmol/mm.min (N = 5; P < 0.025). To assure that the inhibition of sodium flux was due to nitric oxide, another donor, nitroglycerin (2 x 10(-5) M), was used, which decreased sodium flux by 43%. Luminal amiloride (10 microM) decreased net sodium flux by 83% (from 14.8 +/- 1.2 to 2.4 +/- 0.7 pmol/mm.min; N = 5; P < 0.025). The addition of nitric oxide via spermine NONOate to tubules decreased intracellular sodium levels by 26% (N = 6; P < 0.005). The Na(+)-K+ATPase activity of spermine NONOate-treated tubules was 14.7 +/- 3.2 pmol/mm.min compared with the control value of 10.2 +/- 2.0 pmol/mm.min. Nitroglycerin did not significantly affect pump activity either.(ABSTRACT TRUNCATED AT 250 WORDS)