Effects Of DAA-I On Myocardial Ischemia-Reperfusion Injury And Neointima Formation After Angioplasty Of Carotid Artery In Rats

The incidence of myocardial infarction has increased steadily in recent years. It is very important to restore the blood supply after myocardial infarction. But the reperfused blood will casue an inflammation-like reaction, i. e. myocardial ischemia-reperfusion injury. The renin-angiotensin system plays an important role in the pathophysiology of myocardial ischemia-reperfusion injury. Angiotensin II elicits several physiological effects that may exacerbate ischemia-reperfusion injury, i. e. vasoconstriction, positive inotropy and noradrenaline release. Studies suggest a correlation between augmented Ang II and inflammatory response. Recently there were reports that Ang II upregulated ICAM-1 protein expression in rat heart in vivo and in human umbilical vein endothelial cells in vitro. Two Ang II receptor subtypes, the AT, and AT2 receptors, have been i-dentified, and cardiovascular effects of Ang II are mostly generated by an action on the AT, receptor. Both AT, receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce infarct size in myocardial ischemia-reperfusion injury and downregulate the expression of ICAM-1.Percutanous transluminal angioplasty ( PTCA) has become one of the most important treatments for coronary atherosclerotic heart diseases. But restenosis caused by neointima formation after the procedure is a common occurrence. The restenosis of coronary artery after PTCA is an excessive vascular response to the therapeutic procedure. The early response includes migration and hyperplasia ofvascular smooth muscle cells. The precipitation of extracellular matrix is a later reaction. Angiotensin II can exacerbates the restenosis after PTCA through several mechanisms. Hence, control of rennin-angiotensin system will play an important role in the prevention of restenosis after PTCA. It has been approved that AT1 antagonists could prevent the coronary artery from restenosis after PTCA.Des-Aspartate-angiotensin I ( DAA-I) is a nine amino acid peptide. DAA-I has been shown to have a very different profile of effects from Ang II by attenuating the electrically-induced contraction of the rabbit pulmonary artery, inhibiting the central pressor action induced by Ang II and Ang III, decreasing the cardiac hypertrophy in rats with abdominal aortic coarction and reducing hyper-trophic action in cardiomyocytes and hyperplastic action in smooth cells caused by Ang II. These findings suggested that DAA-I is a functional antagonist of angiotensin II. Since angiotensin II plays an important role in myocardial ischemia-reperfusion injury and neointiam formation after angioplasty injury, the present study was set out to investigate the effects of DAA-I on the myocardial ischemic-reperfusion injury and neointiam formation after angioplasty injury in the rats.MethodThe animal model of myocardial ischemia-reperfusion injury was employed in rats. The left coronary artery of anesthetized rats was ligated and the rats were subjected to 45 min of ischemia and 5 h of reperfusion. Various doses of DAA-I were given at 5 min after reperfusion. In order of determine the effects of indo-methacin on the actions of DAA-I, 101 (xmol/kg indomethacin was administered at 30 min before ischemia. Triphenyl tetrozolium chloride-Evans blue technique was employed to determine the effect of DAA-I on infarct size. The change of serum creatine kinase and tissue myeloperxidase activity was also investigated. At same time, the expression of ICAM-1 in myocardial ischemia and reperfusion injury in rats was explored by immunohistochemistry and western blot.In order to determine the effects of DAA-I on the restenosis of artery after angioplasty, the animal model of angioplasty of carotid artery was employed.The Fogarty catheter was introduced into the common carotid artery of rats, and endothelial injury was caused by the movement of the catheter with a capsule blown up with gas for 3 times in the artery. Then the rats were intravenously administered various dose of DAA-I for 13 days. And t...