a Department of Pharmacology, Taishan Medical University, Shandong, ChinaDepartment of Physiology, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, 2-20 Keum-Am-Dong-San, Jeonju 561-180, South KoreaDepartment of Biochemistry, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, South Korea
Angiotensin II type 1 receptor mediates the major cardiovascular effects of Ang II. How-ever, the effects mediated via AT 2 R are still controversial. The aim of the present study is to define the effect of AT 2 R agonist CGP42112A on high stretch-induced ANP secretion and its mechanism using in vitro and in vivo experiments. CGP stimulated high stretch-induced ANP secretion and concentration from isolated perfused rat atria. However, atrial contractility and the translocation of extracellul...更多
Angiotensin II type 1 receptor mediates the major cardiovascular effects of Ang II. How-ever, the effects mediated via AT 2 R are still controversial. The aim of the present study is to define the effect of AT 2 R agonist CGP42112A on high stretch-induced ANP secretion and its mechanism using in vitro and in vivo experiments. CGP stimulated high stretch-induced ANP secretion and concentration from isolated perfused rat atria. However, atrial contractility and the translocation of extracellular fluid did not change. The augmented effect of CGP on high stretch-induced ANP secretion was attenuated by the pretreatment with AT 2 R antagonist or inhibitor for phosphoinositol 3-kinase , nitric oxide , soluble guanylyl cyclase , or protein kinase G . However, antagonist for AT 1 R or Mas receptor did not influence CGP-induced ANP secretion. In vivo study, acute infusion of CGP for 10 min increased plasma ANP level without blood pressure change. In renal hyperten-sive rat atria, AT 2 R mRNA and protein levels were up-regulated and the response of plasma ANP level to CGP infusion in renal hypertensive rats augmented. The pretreatment with AT 2 R antagonist for 10 min followed by CGP infusion attenuated an increased plasma ANP level induced by CGP. However, pretreatment with AT 1 R or Mas receptor antagonist unaffected CGP-induced increase in plasma ANP level. Therefore, we suggest that AT 2 R agonist CGP stimulates high stretch-induced ANP secretion through PI3K/NO/sGC/PKG pathway and these effects are augmented in renal hypertensive rats.收起
