Abstract
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 ...
Abstract
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.
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