Angiotensin-(1-7) upregulates central nitric oxide synthase in spontaneously hypertensive rats

CERRATO BD, FRASCH AP, NAKAGAWA P, LONGO-CARBAJOSA N, PEÑA C, HÖCHT C, GIRONACCI MM

BRAIN RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2012 vol. 1453 p. 1 - 7

0006-8993

Increased blood pressure in hypertension is hypothesized to be caused by high sympatheticnervous system (SNS) activity. Since Ang (1?7) exerts an inhibitory neuromodulatory effecton the SNS through a NO-mediated mechanism, we tested the hypothesis that Ang (1?7) alterscentrally nitric oxide synthase (NOS) activity and expression in spontaneously hypertensiverats (SHR). Since NOS activity is altered in relation to the development ofhypertension in rats, we evaluated the effect of Ang-(1?7) on hypothalamic NOS activityin two different ages in SHR, corresponding to a prehypertensive phase (3?4 weeks) and aestablished hypertension (13?14 weeks) and compared with age-matched Wistar-Kyoto(WKY) rats. NOS activity was measured by the conversion of [3H]L-arginine to citrulline .Ang-(1?7) caused an impairment in NOS activity in prehypertensive SHR (26±4% reduction),while it induced an increase in NOS activity at established hypertension (48±9% increase).In contrast, Ang-(1?7) did not modify NOS activity in age-matched WKY rats. In another set of experiments, Ang-(1?7) was injected into the anterior hypothalamic area, mean arterial blood pressure (MAP) was registered and after 30, 60 and 180 min nNOS expression was evaluated by Western-blot. Ang-(1?7) decreased MAP after 10 min of injection and this effect was blocked by a NOS inhibitor. nNOS expression increased after 180 min of Ang-(1?7) intrahypothalamic injection in both WKY and SHR (WKY: 3.6-fold increase above basal; SHR: 1.85-fold increase above basal). Our results suggest that Ang-(1?7) upregulates hypothalamic NOS in a hypertensive state as a compensatory and protective mechanism to combat hypertension.