Favorable Vascular Actions of Angiotensin–(1–7) in Human ObesityNovelty and Significance [Renin-Angiotensin System]

Obese patients have vascular dysfunction related to impaired insulin-stimulated vasodilation and increased endothelin-1–mediated vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting enzyme 2 product Ang-(1–7) has shown to exert cardiovascular and metabolic benefits in experimental models through stimulation of the Mas receptor. We, therefore, examined the effects of exogenous Ang-(1–7) on vasodilator tone and endothelin-1–dependent vasoconstriction in obese patients. Intra-arterial infusion of Ang-(1–7) (10 nmol/min) resulted in significant increase in unstimulated forearm flow (P=0.03), an effect that was not affected by the Mas receptor antagonist A779 (10 nmol/min; P>0.05). In the absence of hyperinsulinemia, however, forearm flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during Ang-(1–7) administration compared with saline (both P>0.05). During infusion of regular insulin (0.15 mU/kg per minute), by contrast, endothelium-dependent vasodilator response to acetylcholine was significantly enhanced by Ang-(1–7) (P=0.04 versus saline), whereas endothelium-independent response to sodium nitroprusside was not modified (P=0.91). Finally, Ang-(1–7) decreased the vasodilator response to endothelin A receptor blockade (BQ-123; 10 nmol/min) compared with saline (6±1% versus 93±17%; P
Source: Hypertension - Category: Cardiology Authors: Tags: Hypertension, Vascular Disease Original Articles Source Type: research