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 angiotensinconverting 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<0.001); nitric oxide inhibition by l-N-monomethylarginine (4 uμmol/min) during concurrent endothelin A antagonism resulted in similar vasoconstriction in the absence or presence of Ang-(1-7 Ang-(1-7) (P=0.69). Our findings indicate that in obese patients Ang-(1-7) has favorable effects not only to improve insulin-stimulated endotheliumdependent vasodilation but also to blunt endothelin-1-dependent vasoconstrictor tone. These findings provide support for targeting Ang-(1-7) to counteract the hemodynamic abnormalities of human obesity.

Schinzari, F., Tesauro, M., Veneziani, A., Mores, N., Di Daniele, N., Cardillo, C., Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity, <<HYPERTENSION>>, 2018; 2018 (71): 185-191. [doi:10.1161/HYPERTENSIONAHA.117.10280] [http://hdl.handle.net/10807/140407]

Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity

Schinzari, Francesca;Veneziani, Augusto;Mores, Nadia;Cardillo, Carmine
2018

Abstract

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 angiotensinconverting 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<0.001); nitric oxide inhibition by l-N-monomethylarginine (4 uμmol/min) during concurrent endothelin A antagonism resulted in similar vasoconstriction in the absence or presence of Ang-(1-7 Ang-(1-7) (P=0.69). Our findings indicate that in obese patients Ang-(1-7) has favorable effects not only to improve insulin-stimulated endotheliumdependent vasodilation but also to blunt endothelin-1-dependent vasoconstrictor tone. These findings provide support for targeting Ang-(1-7) to counteract the hemodynamic abnormalities of human obesity.
Inglese
Schinzari, F., Tesauro, M., Veneziani, A., Mores, N., Di Daniele, N., Cardillo, C., Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity, <>, 2018; 2018 (71): 185-191. [doi:10.1161/HYPERTENSIONAHA.117.10280] [http://hdl.handle.net/10807/140407]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/140407
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