Adrenomedullin infusion during ischemia/reperfusion attenuates left ventricular remodeling and myocardial fibrosis in rats.
Recent studies have demonstrated that the activation of protein kinase Akt attenuates myocardial ischemia/reperfusion injury. However, it remains unknown whether adrenomedullin (AM), which is also a potent Akt activator, has cardioprotective effects after ischemia/reperfusion. In the present study, Sprague-Dawley rats were exposed to a 30-min period of ischemia induced by ligation of the left coronary artery followed by 24-h reperfusion. They were randomized to receive intravenous administration of AM (0.05 microg/kg/min) or saline for 60 min after coronary ligation. We examined the hemodynamics and myocardial apoptosis 24 h after ischemia/reperfusion. Echocardiographic measurements were performed 4 weeks after ischemia/reperfusion. Myocardial infarct size was also measured histologically. AM significantly reduced left ventricular (LV) end-diastolic pressure (17 +/- 2 to 8 +/- 2 mmHg, p < 0.05) and the number of apoptotic nuclei in myocytes (387 +/- 39 to 147 +/- 72 per field, p < 0.05). AM significantly increased LV dP/dt(max) (4,803 +/- 228 to 5,672 +/- 199 mmHg/s, p < 0.05). AM significantly increased LV fractional shortening (23 +/- 2 vs. 28 +/- 2%, p < 0.05), and significantly reduced LV diastolic dimension (7.4 +/- 0.1 to 6.9 +/- 0.1 mm, p < 0.05) and myocardial infarct size (33 +/- 2 to 20 +/- 2%, p < 0.01) 4 weeks after ischemia/reperfusion. In conclusion, AM infusion during ischemia/reperfusion attenuated the development of LV remodeling and myocardial fibrosis in rats. Based on these results, the cardioprotective effects of AM may be attributed at least partly to its anti-apoptotic effect.
Okumura
Hiroyuki
H
Department of Biochemistry, National Cardiovascular Center Research Institute, Suita, Japan.
Nagaya
Noritoshi
N
Kangawa
Kenji
K
D053607:Adrenomedullin; D000818:Animals; D001011:Aorta; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005355:Fibrosis; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000187:drug effects*
D002316:Cardiotonic Agents; D010455:Peptides; D053607:Adrenomedullin