Impact of acute myocardial ischemia reperfusion on the tissue and blood-borne renin–angiotensin system

Abstract

We examined the impact of acute myocardial ischemia followed by reperfusion (AMI-R) on local and circulating renin-angiotensin system (RAS) in a swine model. The mid left anterior descending artery (n = 6) was occluded for 1 h, followed by reperfusion for 2 h. Monastryl blue/triphenyl tetrazolium chloride staining identified the area-at-risk (AAR) and infarction. A second group of control animals underwent sham operations (C: n = 4). Myocardial expression of angiotensinogen (AGT), renin, chymase, angiotensin converting enzyme (ACE), angiotensin II (Ang II), Ang II type1 receptor (AT1R) and Ang II type 2 receptor (AT2R) in the AAR and the non-ischemic left ventricle (NLV) was assessed. Serum level of these proteins at baseline and at the end of reperfusion was also examined. Chymase (P < 0.05), ACE (P < 0.05), Ang II (P < 0.05), AT1R (P < 0.05) and AT2R (P < 0.05) expressions were found to be significantly higher in the AAR compared to the NLV and C whereas no significant differences were found for AGT (P = 0.58) and renin (P = 0.38). Serum concentration of ACE was significantly higher at the end of reperfusion than at baseline (P < 0.01), whereas no significant difference was found for chymase (P = 0.71), AGT (P = 0.57) and Ang II (P = 0.19). Immunohistochemistry of myocardial sections demonstrated significantly higher expression of ACE (P = 0.02), AT1R (P = 0.01), AT2R (P = 0.02) and Ang II (P < 0.01) in the AAR as compared to the NLV, whereas no significant difference was found for renin (P = 0.39). In conclusion, AMI-R resulted in significantly higher expression of specific cardiac RAS components in AAR compared to the NLV in the acute period.