Author:
Stegbauer Johannes,Kuczka Yvonne,Vonend Oliver,Quack Ivo,Sellin Lorenz,Patzak Andreas,Steege Andreas,Langnaese Kristina,Rump Lars Christian
Abstract
Nitric oxide (NO) is mainly generated by endothelial NO synthase (eNOS) or neuronal NOS (nNOS). Recent studies indicate that angiotensin II generates NO release, which modulates renal vascular resistance and sympathetic neurotransmission. Experiments in wild-type [eNOS(+/+) and nNOS(+/+)], eNOS-deficient [eNOS(−/−)], and nNOS-deficient [nNOS(−/−)] mice were performed to determine which NOS isoform is involved. Isolated mice kidneys were perfused with Krebs-Henseleit solution. Endogenous norepinephrine release was measured by HPLC. Angiotensin II dose dependently increased renal vascular resistance in all mice species. EC50and maximal pressor responses to angiotensin II were greater in eNOS(−/−) than in nNOS(−/−) and smaller in wild-type mice. The nonselective NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME; 0.3 mM) enhanced angiotensin II-induced pressor responses in nNOS(−/−) and wild-type mice but not in eNOS(−/−) mice. In nNOS(+/+) mice, 7-nitroindazole monosodium salt (7-NINA; 0.3 mM), a selective nNOS inhibitor, enhanced angiotensin II-induced pressor responses slightly. Angiotensin II-enhanced renal nerve stimulation induced norepinephrine release in all species. l-NAME (0.3 mM) reduced angiotensin II-mediated facilitation of norepinephrine release in nNOS(−/−) and wild-type mice but not in eNOS(−/−) mice. 7-NINA failed to modulate norepinephrine release in nNOS(+/+) mice. (4-Chlorophrnylthio)guanosine-3′, 5′-cyclic monophosphate (0.1 nM) increased norepinephrine release. mRNA expression of eNOS, nNOS, and inducible NOS did not differ between mice strains. In conclusion, angiotensin II-mediated effects on renal vascular resistance and sympathetic neurotransmission are modulated by NO in mice. These effects are mediated by eNOS and nNOS, but NO derived from eNOS dominates. Only NO derived from eNOS seems to modulate angiotensin II-mediated renal norepinephrine release.
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology
Cited by
25 articles.
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