Stimulation of Angiotensin II Type 2 Receptor Recruit Skeletal and Cardiac Muscle Microvasculature in Humans

Purpose: Acute angiotensin II (Ang II) type 1 receptor (AT 1 R) blockade recruits skeletal and cardiac muscle microvasculature in healthy humans without altering insulin-mediated whole-body glucose disposal. We aimed to elucidate the vascular and metabolic effects of Ang II type 2 receptor (AT 2 R) stimulation in healthy humans. Methods: Following AT 1 R blockade with candesartan, healthy adults received an intravenous infusion of either Ang II or saline for 180 minutes with or without a euglycemic hyperinsulinemic clamp superimposed during the final 120 minutes. Skeletal and cardiac muscle microvascular perfusion, brachial artery diameter and flow velocity, augmentation index, pulse wave velocity (PWV) and insulin-mediated whole-body glucose disposal were assessed. Results: In the presence of AT 1 R blockade, Ang II infusion did not alter hemodynamic parameters or insulin-mediated whole-body glucose disposal. Both insulin and Ang II increased skeletal and cardiac muscle microvascular perfusion; however, superimposing insulin on Ang II infusion did not further augment microvascular perfusion in either tissue. Infusion of Ang II, insulin, or their combination significantly increased total brachial artery blood flow. Ang II infusion increased PWV, an effect attenuated by insulin. Main conclusions: Selective stimulation of AT 2 R significantly enhanced skeletal and cardiac muscle microvascular perfusion and total tissue blood flow without altering insulin’s vascular and metabolic actions in healthy humans. These findings may help explain the cardiovascular and metabolic benefits observed in individuals treated with AT 1 R blockers.