AT2 receptor-dependent vasodilation is mediated by activation of vascular kinin generation under flow conditions

1 Physiological roles of angiotensin II type 2 receptor (AT(2)) are not well defined, This study was designed to investigate the mechanisms of AT(2)-dependent vascular relaxation by studying vasodilation in pressurized and perfused rat mesenteric arterial segments. 2 Perfusion of angiotensin II in the presence of AT(1) antagonist elicited vascular relaxation, which was completely dependent on AT(2) receptors on endothelium. FR173657 (>1 mum), a bradykinin (BK) B-2-Specific antagonist, significantly suppressed AT(2)-dependent vasodilation (maximum inhibition: 68.5% at 10 muM). 3 Kininogen-deficient Brown Norway Katholiek rats showed a significant reduction in AT(2)-mediated vasodilatory response compared with normal wild-type Brown Norway rats. 4 Indomethacin (> 1 muM), aprotinin (10 muM) and soybean trypsin inhibitor (10 muM) also reduced AT(2)-dependent vasodilation. 5 Our results demonstrated that stimulation of AT(2) receptors caused a significant vasodilation through local production of BK in resistant arteries of rat mesentery in a flow-dependent manner. Such vasodilation counterbalances AT(1)-dependent vasoconstriction to regulate the vascular tone.