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

Abstract

Angiotensin II (Ang II) and apoptosis contribute significantly to myocardial ischemia-reperfusion (I-R) injury. Evidence indicates that Ang II may activate apoptosis in myocytes. The present study was undertaken to investigate the effects of angiotensin receptor blockers (ARBs), candesartan, on the apoptosis of cardiac myocytes in rats after I-R. Rats were divided into a control group, a candesartan group I (0.015 mg/kg), and a candesartan group II (0.03 mg/kg). Candesartan was intravenously administered 30 min before ischemia. All rats were subjected to 30 min of coronary occlusion followed by 3 h of reperfusion. The data showed that left ventricular (LV) systolic pressure and LV +dp/dt was decreased after administration of candesartan, but increased after reperfusion in the candesartan group II, compared with those in the candesartan group I and control group. LV -dp/dt was decreased after candesartan administration in candesartan group II. The number of apoptotic cells in the candesartan groups (497+/-204 and 543+/-254, respectively) was higher than that in the control group (287+/-166; p<0.05). There was no significant difference in infarct size among the three groups. However, plasma CPK was lower in the candesartan groups than in the control group. Northern blot analysis showed that p53 mRNA was upregulated in the candesartan groups, in association with increased expression of bax mRNA. Immunohistochemical analysis showed that p53 and bax immunoreactivity were increased in both of the candesartan groups. In conclusion, candesartan increased apoptosis in the rat hearts after acute I-R, and this increase was possibly mediated by upregulation of p53 and bax gene expressions. In addition, candesartan was shown to improve LV function, in association with reduction of CPK release.

• Authors: M Chen, M Hamada, G Hiasa, M Suzuki, S Ikeda, K Hiwada
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 24 Issue 3 Pg. 323-9 (May 2001) ISSN: 0916-9636 [Print] England
• PMID: 11409658 (Publication Type: Journal Article)

Chemical References

• Angiotensin Receptor Antagonists
• Antihypertensive Agents
• Bax protein, rat
• Benzimidazoles
• Biphenyl Compounds
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• Receptor, Angiotensin, Type 1
• Tetrazoles
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• Creatine Kinase
• candesartan

Topics

• Acute Disease
• Angiotensin Receptor Antagonists
• Animals
• Antihypertensive Agents (pharmacology)
• Apoptosis (drug effects)
• Benzimidazoles (pharmacology)
• Biphenyl Compounds
• Blotting, Northern
• Creatine Kinase (blood)
• Gene Expression (drug effects)
• Heart Rate (drug effects)
• Hypertension (drug therapy)
• Immunohistochemistry
• Male
• Myocardial Reperfusion Injury (pathology)
• Myocardium (chemistry, pathology)
• Proto-Oncogene Proteins (analysis, genetics)
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• Receptor, Angiotensin, Type 1
• Tetrazoles (pharmacology)
• Tumor Suppressor Protein p53 (analysis, genetics)
• Ventricular Pressure (drug effects)
• bcl-2-Associated X Protein