AT 2 receptor‐mediated vasodilation in the mouse heart depends on AT 1A receptor activation

1 Angiotensin (Ang) II type 2 (AT 2 ) receptors are believed to counteract Ang II type 1 (AT 1 ) receptor‐mediated effects. Here, we investigated AT 2 receptor‐mediated effects on coronary and cardiac contractility in C57BL/6 mice. 2 Hearts were perfused according to Langendorff. Baseline coronary flow (CF) and left ventricular systolic pressure (LVSP) were 2.7±0.1 ml min −1 and 111±3 mmHg ( n =50), respectively. 3 Ang II ( n =14) concentration dependently decreased CF and LVSP, by maximally 41±4 and 25±3%, respectively (pEC 50 s 7.41±0.12 and 7.65±0.12). The AT 1 receptor antagonist irbesartan ( n =4) abolished all Ang II‐induced changes, whereas the AT 2 receptor antagonist PD123319 ( n =6) enhanced ( P <0.05) the effect of Ang II on CF (to 59±1%) and LVSP (to 44±2%), without altering its potency. A similar enhancement was observed in the presence of nitric oxide (NO) synthase inhibitor N ω ‐nitro‐ L ‐arginine methyl ester HCl ( L ‐NAME; n =4). On top of L ‐NAME, PD123319 no longer affected the response to Ang II ( n =4). 4 The AT 2 receptor agonist CGP42112A ( n =4) did not affect CF or LVSP, nor did CGP42112A ( n =4) alter the constrictor response to the α 1 ‐adrenoceptor agonist phenylephrine. Furthermore, Ang II exerted no effects in hearts of AT 1A −/− mice ( n =5), whereas its effects in hearts of AT 1A +/+ wild‐type control mice ( n =7) were indistinguishable from those in hearts of C57BL/6 mice. 5 In conclusion, Ang II exerts opposite effects on coronary and cardiac contractility in the mouse heart via activation of AT 1A and AT 2 receptors. AT 2 receptor‐mediated effects depend on NO and occur only in conjunction with AT 1A receptor activation.British Journal of Pharmacology (2006) 148 , 452–458. doi: 10.1038/sj.bjp.0706762