Endothelin-1 production by rat inner medullary collecting duct: effect of nitric oxide, cGMP, and immune cytokines.
Nitric oxide (NO), guanosine 3',5'-cyclic monophosphate (cGMP), and endothelin-1 (ET-1) inhibit collecting duct sodium reabsorption. Because the inner medullary collecting duct (IMCD) synthesizes NO and ET-1, we examined NO and cGMP regulation of IMCD ET-1 production. S-nitroso-N-acetylpenicillamine (SNAP, 6 h) increased NO and cGMP and modestly reduced ET-1 release in cultured rat IMCD. Atrial natriuretic peptide or dibutyryl cGMP (6 h exposure to each) also mildly decreased IMCD ET-1 release. In long-term exposure studies, IMCD cells were incubated with tumor necrosis factor (TNF) and interferon-gamma (IFN) up to 72 h. IFN/TNF increased NO and cGMP production while reducing ET-1 release by 84%; N-monomethyl-L-arginine inhibited this effect only marginally, suggesting NO was not primarily involved. IFN alone greatly reduced IMCD ET-1 release and ET-1 mRNA levels. These data indicate that short- and long-term increases in NO and cGMP modestly reduce IMCD ET-1 production. Additionally, IFN potently inhibits IMCD ET-1 release by an undetermined mechanism.
Kohan
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DE
Division of Nephrology, Department of Veterans Affairs Medical Center, Salt Lake City, Utah.
Padilla
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001483:Base Sequence; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D017931:DNA Primers; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology*; D016232:Endothelins / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology*; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine
D017931:DNA Primers; D016232:Endothelins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; D026423:S-Nitroso-N-Acetylpenicillamine; D007371:Interferon-gamma; D009320:Atrial Natriuretic Factor; D001120:Arginine; D010396:Penicillamine; D006152:Cyclic GMP