Comparison of the cardiac effects between quinazoline-based alpha1-adrenoceptor antagonists on occlusion-reperfusion injury.
Quinazoline-based compounds such as prazosin and its congeners including doxazosin, bunazosin, and terazosin are widely used as antihypertensive agents. However, there were many clinical observations showing that using these agents may result in higher risk of cardiovascular accidents in recent years. In this study, we compared the effects of four alpha-adrenoceptor antagonists: prazosin, doxazosin, bunazosin, and terazosin on occlusion-reperfusion injury. Langendorff-perfused rat hearts were pretreated with these four antagonists, and then the left main coronary artery was occluded. After 30 min occlusion, the hearts were reperfused for 2 h and the infarct sizes were measured. Two of the compounds studied, prazosin and doxazosin, apparently increased infarct size, CK-MB, and LDH activities after 2 h reperfusion. In contrast, bunazosin decreased infarct size and those biochemical indicators of cellular damage compared to control hearts. Although infarct size after reperfusion was differently changed by these four alpha-adrenoceptor antagonists, TUNEL-positive nuclei and caspase-3 protein expressions of all the groups were not significantly different. We supposed that the different effects of these four agents on infarct size came from the difference in necrosis rather than apoptosis.
Lee
An-Sheng
AS
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan ROC.
Su
Ming-Jai
MJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar
D000317:Adrenergic alpha-Antagonists; C505410:Casp3 protein, rat; D053148:Caspase 3