The Activation Of The Local Intracardiac Renin-angiotensin System And Subsequent Influence On Cardiac Function After Myocardial Ischemia-reperfusion, And Myocardial Infarction In Rats

Severe myocardial ischemia results in a number of events, including depletion of high-energy phosphate stores, intracellular acidification, disturbance of ionic homeostasis, and membrane damage ultimately leading to the cell. The only way to salvage ischemic myocardium is by timely re-establishment of coronary flow. However, the reperfusion after a long period of ischemia may result in a more depression of cardiac mechanical performance. Therefore, the time of ischemia is a most important factor to determine the extents of ischemia-reperfusion injury. There is now evidence that the release of some local endocrine factors induced by ischemia itself are known to increase ischemia-reperfusion injury. The local intracardiac renin-angiotensin system (RAS) may be one of them. A possible role of the local intracardiac RAS in the pathogenesis of myocardial ischemia-reperfusion insult has been postulated because of cardioprotective effect observed with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor 1 (AT₁) antagonist, but is in controversy due to the lack of direct evidence on the changes of the local intracardiac RAS, especially of their elements mRNA expressions, after myocardial ischemia and reperfusion. Otherwise, there continue to be many grounds for uncertainty as to the role of ACEI and AT₁ receptor antagonist because some investigators hadn't found any beneficial effects of these drugs on myocardial ischemia and reperfusion injury. The present study was performed in isolated perfused rat hearts, by means of cardiac mechanical measurement, biochemical analysis, and molecular biological techniques, to determine whether the local intracardiac RAS is involved in the process of myocardial ischemia-reperfusion injury, meanwhile, to evaluate the potency of the non-peptide AT₁ receptor antagonist, Losartan, and Trandolaprilat, an active form of Trandolapril, a comparatively-new ACEI with a high affinity for ACE that results in a slow dissociation and a long-lasting ACE inhibitory effect.Ventricular remodeling has been coined to describe a succession of morphological changes which occur following myocardial infarction and which results, eventually, in progressive dilatation and dysfuntion of the ventricle. This process encompasses not only the infarcted segments, but, notably, also the non-infarcted portions of the ventricle. Left ventricular enlargement can occur as a result of infarct expansion, which gradually...