Permissive role of nitric oxide in macula densa control of renin secretion

• Published in: American journal of physiology. Renal physiology Vol. 55; no. 5; pp. F848 - F857
• Main Authors: CASTROP, Hayo, SCHWEDA, Frank, MIZEL, Diane, YUNING HUANG, BRIGGS, Josie, KURTZ, Armin, SCHNERMANN, Jurgen
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.05.2004
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Kidneys; Nitric oxide; Proteases; Rodents; Vertebrates: urinary system; Sulfanilamide derivatives; perfused kidney; neuronal nitric oxide synthase knockout; endothelial nitric oxide synthase knockout; furosemide; bumetanide; Sulfonamide; Enzyme; Secretion; plasma renin; isolated; Furosemide; Nitric-oxide synthase; Kidney; Peptidases; Vertebrata; Mammalia; Renin; Urinary system; Nitric oxide; Anthranilic acid derivatives; Hydrolases; Aspartic endopeptidases; Oxidoreductases; Mutation; Bumetanide; Macula densa
• ISSN: 1931-857X; 1522-1466

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 X kg-1 X 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 Nomega-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 plus or minus 28 vs. 355 plus or minus 57 ng ANG I X ml-1 X 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. [PUBLICATION ABSTRACT]