An angiotensin II type 1 receptor blocker, candesartan, increases myocardial apoptosis in rats with acute ischemia-reperfusion

Angiotensin II(Ang II) and apoptosis contribute significantly to myocardial ischemia-reperfusion (I-R) injury. Evidence indicates that Ang II may acti vate apoptosis in myocytes. The present study was undertaken to investigate the effects of angiotensin receptor blockers (ARBs), candesartan, on the a poptosis of cardiac myocytes in rats after I-R, Rats were divided into a co ntrol group, a candesartan group I (0.015 mg/kg), and a candesartan group I I (0.03 mg/kg). Candesartan was intravenously administered 30 min before is chemia, All rats were subjected to 30 min of coronary occlusion followed by 3 h of reperfusion. The data showed that left ventricular (LV) systolic pr essure and LV +dp/dt was decreased after administration of candesartan, but increased after reperfusion in the candesartan group II, compared with tho se in the candesartan group I and control group. LV -dp/dt was decreased af ter candesartan administration in candesartan group II. The number of apopt otic cells in the candesartan groups (497 +/- 204 and 543 +/- 254, respecti vely) was higher than that in the control group (287 +/- 166; p <0.05). The re was no significant difference in infarct size among the three groups. Ho wever, plasma CPK was lower in the candesartan groups than in the control g roup. Northern blot analysis showed that p53 mRNA was upregulated in the ca ndesartan groups, in association with increased expression of bar mRNA. Imm unohistochemical analysis showed that p53 and bar immunoreactivity were inc reased in both of the candesartan groups. In conclusion, candesartan increa sed apoptosis in the rat hearts after acute I-R, and this increase was poss ibly mediated by upregulation of p53 and bar gene expressions. In addition, candesartan was shown to improve LV function, in association with reductio n of CPK release.