Adrenomedullin infusion during ischemia/reperfusion attenuates left ventricular remodeling and myocardial fibrosis in rats.

Abstract

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.

• Authors: Hiroyuki Okumura, Noritoshi Nagaya, Kenji Kangawa
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 26 Suppl Pg. S99-104 (Feb 2003) ISSN: 0916-9636 [Print] England
• PMID: 12630818 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Peptides
• Adrenomedullin

Topics

• Adrenomedullin
• Animals
• Aorta
• Apoptosis (drug effects)
• Blood Pressure (drug effects)
• Cardiotonic Agents (pharmacology)
• Fibrosis
• Male
• Myocardial Infarction (drug therapy, pathology)
• Myocardial Reperfusion Injury (drug therapy, pathology)
• Myocardium (pathology)
• Peptides (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Ventricular Remodeling (drug effects)