Complete blockade of the vasorelaxant effects of Ang-(1-7) and bradykinin in murine microvessels by antagonists of the receptor Mas

Autor: Peiró, Concepción, Vallejo, Susana, Gembardt, Florian, Palacios, Erika, Novella, Susana, Azcutia, Verónica, Rodríguez-Mañas, Leocadio, Hermenegildo, Carlos, Sánchez-Ferrer, Carlos F., Walther, THOMAS
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Peiró, Concepción Vallejo, Susana Gembardt, Florian Palacios, Erika Novella, Susana Azcutia, Verónica Rodríguez-Mañas, Leocadio Hermenegildo, Carlos Sánchez-Ferrer, Carlos F. Walther, THOMAS 2013 Complete blockade of the vasorelaxant effects of Ang-(1-7) and bradykinin in murine microvessels by antagonists of the receptor Mas. Journal of Physiology-London 591 9 2275 2285
RODERIC. Repositorio Institucional de la Universitat de Valéncia
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RODERIC: Repositorio Institucional de la Universitat de Valéncia
Popis: The heptapeptide angiotensin-(1-7) is a biologically active metabolite of angiotensin II, the predominant peptide of the renin-angiotensin system. Recently, we have shown that the receptor Mas is associated with angiotensin-(1-7)-induced signalling and mediates, at least in part, the vasodilatory properties of angiotensin-(1-7). However, it remained controversial whether an additional receptor could account for angiotensin-(1-7)-induced vasorelaxation. Here, we used two different angiotensin-(1-7) antagonists, A779 and d-Pro-angiotensin-(1-7), to address this question and also to study their influence on the vasodilatation induced by bradykinin. Isolated mesenteric microvessels from both wild-type and Mas-deficient C57Bl/6 mice were precontracted with noradrenaline, and vascular reactivity to angiotensin-(1-7) and bradykinin was subsequently studied using a small-vessel myograph. Furthermore, mechanisms for Mas effects were investigated in primary human umbilical vein endothelial cells. Both angiotensin-(1-7) and bradykinin triggered a concentration-dependent vasodilatation in wild-type microvessels, which was absent in the presence of a nitric oxide synthase inhibitor. In these vessels, the pre-incubation with the Mas antagonists A779 or d-Pro-angiotensin-(1-7) totally abolished the vasodilatory capacity of both angiotensin-(1-7) and bradykinin, which was nitric oxide mediated. Accordingly, Mas-deficient microvessels lacked the capacity to relax in response to either angiotensin-(1-7) or bradykinin. Pre-incubation of human umbilical vein endothelial cells with A779 prevented bradykinin-mediated NO generation and NO synthase phosphorylation at serine 1177. The angiotensin-(1-7) antagonists A779 and d-Pro-angiotensin-(1-7) equally block Mas, which completely controls the angiotensin-(1-7)-induced vasodilatation in mesenteric microvessels. Importantly, Mas also appears to be a critical player in NO-mediated vasodilatation induced by renin-angiotensin system-independent agonists by altering phosphorylation of NO synthase.
Databáze: OpenAIRE
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