title: 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 (AT(1)R) and vasodilatation through the type 2 receptor (AT(2)R). 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 AT(1)R 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 AT(2)R antagonist PD123319 significantly decreased muscle MBV by >or=80% (P<0.001). This was associated with a significant decrease in hindleg glucose extraction and muscle oxygen saturation. AT(2)R antagonism and inhibition of NO synthase each blocked the losartan-induced increase in muscle MBV and glucose uptake. In conclusion, angiotensin II acts on both AT(1)R and AT(2)R to regulate basal muscle microvascular perfusion. Basal AT(1)R tone restricts muscle MBV and glucose extraction, whereas basal AT(2)R activity increases muscle MBV and glucose uptake. Pharmacological manipulation of the balance of AT(1)R and AT(2)R activity affords the potential to improve glucose metabolism.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, Va 22908, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Chai
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Barrett
authors.forename: Robert M
authors.initials: RM
authors.lastname: Carey
authors.forename: Wenhong
authors.initials: W
authors.lastname: Cao
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D001795:Blood Pressure Determination; D001810:Blood Volume / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D007093:Imidazoles / Q000494:pharmacology; D007262:Infusions, Intravenous; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D011336:Probability; D011725:Pyridines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D007093:Imidazoles; D011725:Pyridines; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan