Effects of angiotensin II type 2 receptor agonist on stretch‐induced ANP secretion via PI 3K/PKG/NO pathway

Abstract

Angiotensin II (Ang II) is well‐known a major peptide of renin‐angiotensin system (RAS) as regulating blood pressure and body fluid volume. It is already known that the AT1 receptor mediates the major cardiovascular effects of Ang II. However, effects mediated via AT2 receptor are still controversial. The aim of the present study is to define the effect of AT2 receptor agonist, CGP 42112A on high stretch‐induced ANP secretion and its mechanism using in vitro and in vivo experiments. CGP 42112A stimulated high stretch‐induced ANP secretion and concentration from isolated perfused rat atria. The augmented effect of CGP42112A (0.1 μM) on high stretch‐induced ANP secretion was attenuated by the pretreatment with AT2 receptor antagonist or inhibitor for phosphoinositol 3‐kinase (PI3K), nitric oxide (NO), soluble guanylyl cyclase (sGC), or protein kinase G (PKG). However antagonist for AT1 or Mas receptor tended to augment the effect of CGP 42112A on high stretch‐induced ANP secretion. In vivo study, acute infusion of CGP 42112A for 10 min increased plasma ANP level without blood pressure change and pretreatment with losartan for 10 min followed by CGP 42112A infusion increased plasma ANP level more than CGP 42112A alone. In hypertensive atria, AT2 receptor mRNA and protein level were up‐regulated. The response of plasma ANP level by acute infusion of CGP 42112A in hypertensive rat augmented. Therefore, we suggest that AT2 receptor agonist stimulates high stretch‐induced ANP secretion through PI3K/NO/sGC/PKG pathway.Supported by the National Research Foundation (2012–0009322)