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)
Stoos
B A
BA
Department of Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.
Garcia
N H
NH
Garvin
J L
JL
D000042:Absorption; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000378:metabolism*; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D009589:Nitrogen Oxides; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives / Q000378:metabolism
D009589:Nitrogen Oxides; D015222:Sodium Channels; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; D000584:Amiloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase