Angiotensin-(1-7) recruits muscle microvasculature and enhances insulin's metabolic action via mas receptor.
Angiotensin-(1-7) recruits muscle microvasculature and enhances insulin's metabolic action via mas receptor.
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DOI：
10.1161/hypertensionaha.113.03025
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Fu Z;Zhao L;Aylor KW;Carey RM;Barrett EJ;Liu Z
Angiotensin (Ang)-(1-7), an endogenous ligand for the G protein-coupled receptor Mas, exerts both vasodilatory and insulin sensitizing effects. In skeletal muscle relaxation of pre-capillary arterioles recruits microvasculature and increases the endothelial surface area available for nutrient and hormone exchanges. To assess whether Ang-(1-7) recruits microvasculature and enhances insulin action in muscle, overnight-fasted adult rats received an intravenous infusion of Ang-(1-7) (0, 10 or 100 ng/kg/min) for 150 min with or without a simultaneous infusion of the Mas inhibitor A-779 and a superimposition of a euglycemic insulin clamp (3 mU/kg/min) from 30 to 150 min. Hindlimb muscle microvascular blood volume (MBV), microvascular flow velocity (MFV) and microvascular blood flow (MBF) were determined. Myographic changes in tension were measured on pre-constricted distal saphenous artery. Ang-(1-7) dose-dependently relaxed the saphenous artery (p<0.05) ex vivo. This effect was potentiated by insulin (p<0.01) and abolished by either endothelium denudement or Mas inhibition. Systemic infusion of Ang-(1-7) rapidly increased muscle MBV and MBF (p<0.05, each) without altering MFV. Insulin infusion alone increased muscle MBV by 60–70% (p<0.05). Adding insulin to the Ang-(1-7) infusion further increased muscle MBV and MBF (~2.5 fold, p<0.01). These were associated with a significant increase in insulin-mediated glucose disposal and muscle Akt and ERK1/2 phosphorylation. A-779 pre-treatment blunted Ang-(1-7)’s microvascular and insulin-sensitizing effects. We conclude that Ang-(1-7) by activating Mas recruits muscle microvasculature and enhances insulin’s metabolic action. These effects may contribute to the cardiovascular protective responses associated with Mas activation and explain Ang-(1-7)’s insulin sensitizing action.
