Angiotensin-(1-7) increased cardiac nitric oxide synthase activity and expression in spontaneously hypertensive rats

GIRONACCI MARIELA; LOPEZ VERRILLI M A; PEÑA CLARA; BALASZCZUK ANA MARÍA; ARRANZ CRISTINA; COSTA MARIA DE LOS ANGELES

Berlín. Alemania.

Congreso; Eighteenth European Meeting on Hypertension.; 2008

European Society of Hypertension. International Society of Hypertension.

Objectives: Angiotensin (Ang) (1-7) is a bioactive compound of the renin-angiotensin system that exerts effects that lead to blood pressure reduction, counterbalancing Ang II pressor actions. Since a cardioprotective role has been suggested for Ang-(1-7) and that many of its effects are not elicited when nitric oxide generation is blocked, we hypothesize that the peptide stimulates cardiac nitric oxide synthase (NOS) activity and expression. Our aim was to investigate the effect of Ang-(1-7) on nitric oxide synthase (NOS) expression and activity in ventricles from spontaneously hypertensive rats (SHR). Methods: Adult male WKY or SHR were infused with Ang-(1-7) (0.35 nmoles/min) during 1 hour and ventricles were isolated to measure eNOS, nNOS and iNOS expression by western-blot. In another set of experiments, ventricules were isolated and slices were incubated with [14C]L-arginine in the absence or presence of Ang-(1-7) for 30 min. After homogenization, the supernatants were passed through a ionic interchange column. [14C]L-citrulline were eluted and measured by liquid scintillation counting. Statistical analysis were performed by one-way ANOVA or Student t test. Results: Ang-(1-7) infusion diminished mean arterial pressure in SHR but not in WKY (SHR: 146±9* vs 180±9 in controls, *p<0.01; WKY: 87±7 vs 90±8 in controls). eNOS content in ventricles from SHR was increased by 67.4±6.4% by Ang-(1-7) infusion, while it was not modified by Ang-(1-7) in WKY. nNOS expression was increased by 51±10% by Ang-(1-7) infusion while iNOS endogenous levels were not modified by the peptide. Increasing concentrations of Ang-(1-7) (10 nM to 1 mM) caused an increase in NOS activity in ventricle from WKY and SHR, showing a more potent action in SHR. The increased NOS activity caused by 100 nM Ang-(1-7) was blocked by Hoe 140 (1 mM), a bradykinin B2 receptor antagonist. Conclusions: Ang-(1-7) increased cardiac NOS expression and activity through a bradykinin-dependent mechanism.