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

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 55; no. 2, Part 2 Suppl; pp. 523 - 530
• Main Authors: Chai, Weidong, Wang, Wenhui, Liu, Jia, Barrett, Eugene J, Carey, Robert M, Cao, Wenhong, Liu, Zhenqi
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.02.2010; Lippincott Williams & Wilkins
• Subjects: Angiotensin II - pharmacology; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Flow Velocity - drug effects; Blood Glucose - metabolism; Blood Pressure Determination; Blood Volume - drug effects; Blood Volume - physiology; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Disease Models, Animal; Imidazoles - pharmacology; Infusions, Intravenous; Losartan - pharmacology; Male; Medical sciences; Microcirculation - physiology; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Probability; Pyridines - pharmacology; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Vasoconstrictor Agents - pharmacology; Hypertension; NO; Peptide hormone; Cardiovascular disease; Glucose; Striated muscle; Metabolism; angiotensin II receptors; microvascular blood volume; Octapeptide; Blood volume; muscle; Angiotensin II; glucose metabolism
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.109.145409

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 the losartan-induced increase in muscle MBV and glucose uptake. In conclusion, angiotensin II acts on both AT1R and AT2R to regulate basal muscle microvascular perfusion. Basal AT1R tone restricts muscle MBV and glucose extraction, whereas basal AT2R activity increases muscle MBV and glucose uptake. Pharmacological manipulation of the balance of AT1R and AT2R activity affords the potential to improve glucose metabolism.