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2014 ; 63
(6
): 1219-27
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Angiotensin-(1-7) recruits muscle microvasculature and enhances insulin s
metabolic action via mas receptor
#MMPMID24711523
Fu Z
; Zhao L
; Aylor KW
; Carey RM
; Barrett EJ
; Liu Z
Hypertension
2014[Jun]; 63
(6
): 1219-27
PMID24711523
show ga
Angiotensin-(1-7) [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 precapillary 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 per minute) for 150 minutes with or
without a simultaneous infusion of the Mas inhibitor A-779 and a superimposition
of a euglycemic insulin clamp (3 mU/kg per minute) from 30 to 150 minutes. Hind
limb muscle microvascular blood volume, microvascular flow velocity, and
microvascular blood flow were determined. Myographic changes in tension were
measured on preconstricted 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 microvascular
blood volume and microvascular blood flow (P<0.05, each) without altering
microvascular flow velocity. Insulin infusion alone increased muscle
microvascular blood volume by 60% to 70% (P<0.05). Adding insulin to the
Ang-(1-7) infusion further increased muscle microvascular blood volume and
microvascular blood flow (?2.5 fold; P<0.01). These were associated with a
significant increase in insulin-mediated glucose disposal and muscle protein
kinase B and extracellular signal-regulated kinase 1/2 phosphorylation. A-779
pretreatment blunted the microvascular and insulin-sensitizing effects of
Ang-(1-7). We conclude that Ang-(1-7) by activating Mas recruits muscle
microvasculature and enhances the metabolic action of insulin. These effects may
contribute to the cardiovascular protective responses associated with Mas
activation and explain the insulin-sensitizing action of Ang-(1-7).