title: Nitric oxide-angiotensin II interactions in angiotensin II-dependent hypertension.
abstract: Many studies indicate that renal haemodynamic function in angiotensin II- (ANG II) dependent hypertension is not reduced as much as would be predicted from the elevated ANG II levels suggesting that counteracting renoprotective mechanisms are activated. One important renoprotective effect is mediated by increased levels of nitric oxide. Recent studies using the ANG II-infused hypertensive rat model have shown that inhibition of nitric oxide synthesis (NOS) causes greater decreases in renal blood flow and glomerular filtration rate in ANG II-infused hypertensive rats than in control rats. This augmented nitric oxide-dependent influence is localized primarily in the cortex and to the preglomerular vasculature. The differential effects on the renal cortex and medulla are also reflected by the differences in NOS activities and protein expression. Ca2+-dependent NOS activity was significantly greater in the cortex but not the medulla of the ANG II-infused hypertensive rats compared with control rats. This was associated with marked activation of endothelial NOS protein levels and smaller increases in neuronal NOS protein levels in the cortex but not in the medulla. In contrast, the Ca2+-independent NOS activity and the inducible NOS protein levels in the cortex were significantly lower in the ANG II-infused hypertensive rats. These data support the hypothesis that cortical Ca2+-dependent NOS, primarily endothelial NOS, is stimulated during the early phases of ANG II-induced hypertension and exerts a renoprotective effect on cortical haemodynamics.
authors.affiliation: Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: L G
authors.initials: LG
authors.lastname: Navar
authors.forename: A
authors.initials: A
authors.lastname: Ichihara
authors.forename: S Y
authors.initials: SY
authors.lastname: Chin
authors.forename: J D
authors.initials: JD
authors.lastname: Imig
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D000804:Angiotensin II; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase