Endogenous angiotensin II modulates nNOS expression in renovascular hypertension.
Nitric oxide (NO) influences renal blood flow mainly as a result of neuronal nitric oxide synthase (nNOS). Nevertheless, it is unclear how nNOS expression is modulated by endogenous angiotensin II, an inhibitor of NO function. We tested the hypothesis that the angiotensin II AT1 receptor and oxidative stress mediated by NADPH oxidase contribute to the modulation of renal nNOS expression in two-kidney, one-clip (2K1C) hypertensive rats. Experiments were performed on male Wistar rats (150 to 170 g body weight) divided into 2K1C (N = 19) and sham-operated (N = 19) groups. nNOS expression in kidneys of 2K1C hypertensive rats (N = 9) was compared by Western blotting to that of 2K1C rats treated with low doses of the AT1 antagonist losartan [10 mg x kg(-1) x day(-1); N = 5] or the superoxide scavenger tempol [0.2 mmol x kg(-1) x day(-1); N = 5], which still remain hypertensive. After 28 days, nNOS expression was significantly increased by 1.7-fold in the clipped kidneys of 2K1C rats and by 3-fold in the non-clipped kidneys of 2K1C rats compared with sham rats, but was normalized by losartan. With tempol treatment, nNOS expression increased 2-fold in the clipped kidneys and 1.4-fold in the non-clipped kidneys compared with sham rats. The changes in nNOS expression were not followed by changes in the enzyme activity, as measured indirectly by the cGMP method. In conclusion, AT1 receptors and oxidative stress seem to be primary stimuli for increased nNOS expression, but this up-regulation does not result in higher enzyme activity.
Pereira
T M C
TM
Laboratório de Transgenes e Controle Cardiovascular, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, 29043-900 Vitória, ES, Brasil.
Balarini
C M
CM
Silva
I V
IV
Cabral
A M
AM
Vasquez
E C
EC
Meyrelles
S S
SS
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000201:enzymology* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019255:NADPH Oxidases / Q000187:drug effects* / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels
D047228:Angiotensin II Type 1 Receptor Blockers; D003497:Cyclic N-Oxides; D013113:Spin Labels; D000804:Angiotensin II; D052248:Nitric Oxide Synthase Type I; D019255:NADPH Oxidases; D019808:Losartan; C001803:tempol