Permissive role of nitric oxide in macula densa control of renin secretion.
Experiments were performed in neuronal (nNOS)- and endothelial nitric oxide synthase (eNOS)-deficient mice to study the role of nitric oxide (NO) in macula densa control of renin secretion in vivo and in the isolated, perfused mouse kidney. Acute and chronic administration of loop diuretics was used as a method to stimulate macula densa-mediated renin secretion. Increases in plasma renin concentration (PRC) in response to a 3-day infusion of bumetanide (50 mg.kg(-1).day(-1)) or an acute injection of furosemide (50 mg/kg ip) were not markedly altered in nNOS-/- mice. Responses to furosemide were also maintained in eNOS-/- mice, but the administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) markedly attenuated the PRC response to furosemide in these mice. In the isolated kidney preparation, bumetanide caused similar relative increases in renin secretion in kidneys of wild-type, nNOS-/-, and eNOS-/- mice. Bumetanide only marginally increased renin secretion in L-NAME-treated kidneys, but the bumetanide effect was normalized by S-nitroso-N-acetyl-penicillamine. Basal PRC was significantly reduced in male nNOS-/- mice compared with nNOS+/+ (189 +/- 28 vs. 355 +/- 57 ng ANG I.ml(-1).h(-1); P = 0.017). There was no significant difference in PRC between eNOS+/+ and eNOS-/- mice. Basal renin secretion rates in perfused kidneys isolated from nNOS-/- or eNOS-/- mice were markedly reduced compared with wild-type controls. Our data suggest that NO generated by macula densa nNOS does not play a specific mediator role in macula densa-dependent renin secretion. However, NO independent of its exact source permits the macula densa pathway of renin secretion to function normally.
Castrop
Hayo
H
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Schweda
Frank
F
Mizel
Diane
D
Huang
Yuning
Y
Briggs
Josie
J
Kurtz
Armin
A
Schnermann
Jurgen
J
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002478:Cells, Cultured; D004232:Diuretics / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D066298:In Vitro Techniques; D007606:Juxtaglomerular Apparatus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008138:Loop of Henle / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012083:Renin / Q000097:blood / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D004232:Diuretics; D004791:Enzyme Inhibitors; D002034:Bumetanide; D009569:Nitric Oxide; D005665:Furosemide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester