Angiotensin II Type 1 and Type 2 Receptors Regulate Basal Skeletal Muscle Microvascular Volume and Glucose Use

Abstract

Angiotensin II causes vasoconstriction via the type 1 receptor (AT1R) and vasodilatation through the type 2 receptor (AT2R). Both are expressed in muscle microvasculature, where substrate exchanges occur. Whether they modulate basal muscle microvascular perfusion and substrate metabolism is not known. We measured microvascular blood volume (MBV), a measure of microvascular surface area and perfusion, in rats during systemic infusion of angiotensin II at either 1 or 100 ng/kg per minute. Each caused a significant increase in muscle MBV. Likewise, administration of the AT1R blocker losartan increased muscle MBV by >3-fold (P<0.001). Hindleg glucose extraction and muscle interstitial oxygen saturation simultaneously increased by 2- to 3-fold. By contrast, infusing AT2R antagonist PD123319 significantly decreased muscle MBV by ≥80% (P<0.001). This was associated with a significant decrease in hindleg glucose extraction and muscle oxygen saturation. AT2R antagonism and inhibition of NO synthase each blocked th...