Changes in cardiac nitric oxide synthase activity and expression induced by angiotensin-(1-7) in spontaneously hypertensive rat

M.M. GIRONACCI, M.A. LOPEZ VERRILLI, C. PEÑA, A. BALAZCZUK, C. ARRANZ, M.A. COSTA

Berlín, Alemania

Simposio; 22nd Scientific Meeting of the International Society of Hypertension; 2008

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:ES; mso-fareast-language:ES;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> 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 with nitric oxide synthase (NOS) inhibitors, we hypothesize that the peptide stimulates cardiac 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). Adult male WKY or SHR were infused with Ang-(1-7) (0.35 nmoles/min) during 1 hour and ventricles were isolated to measure endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) expression by western-blot. In another set of experiments, hearts were isolated and ventricle 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. Ang-(1-7) infusion caused a decrease in mean arterial pressure in SHR but not in WKY rats (WKY rats: 87±7 mmHg in Ang-(1-7)-infused rats vs 90±8 mmHg in saline-infused rats; SHR rats: 146±9* mmHg in Ang-(1-7)-infused rats vs 180±9 mmHg in saline-infused rats, *p