Adrenocorticotrope hormone fragment (4-10) attenuates the ischemia/reperfusion-induced cardiac injury in isolated rat hearts.

Abstract

The aim of our study was to investigate the contribution of the adrenocorticotropic hormone fragment, ACTH (4-10), on the recovery of postischemic cardiac function. Effects of ACTH (4-10) on caspase-3 activity, cardiomyocyte and endothelial apoptosis, and HO-1 protein expression were studied. Rats were treated with various doses of ACTH (4-10), and then 12 h later, anesthetized, hearts were isolated, perfused, and subjected to 30-min ischemia followed by 120-min reperfusion. Cardiac function including heart rate, coronary flow, aortic flow, and left ventricular developed pressure were recorded. After 120-min reperfusion, 200 mug/kg of ACTH (4-10) significantly improved the recovery of aortic flow, coronary flow, and left ventricular developed pressure from their untreated control values of 15.3 +/- 0.9 ml/min, 6.5 +/- 0.9 ml/min, and 10 +/- 0.6 kPa to 20.7 +/- 1.3 ml/min, 24.8 +/- 1.8 ml/min and 13.7 +/- 0.7 kPa, respectively. Heart rate did not show significant changes during reperfusion. ACTH (4-10) treatment resulted in a reduction in infarct size, caspase 3 activity, apoptosis, and an increase in HO-1 expression. When ACTH (4-10) was given at the moment of reperfusion, the drug failed to improve the postischemic recovery of the myocardium. Thus, ACTH (4-10) can be a useful tool for the prevention of the development of ischemia/reperfusion-induced injury.

• Authors: Bela Juhasz, Peter Der, Peter Szodoray, Rudolf Gesztelyi, Istvan Lekli, Istvan Bak, Miklos Antal, Nilanjana Maulik, Arpad Tosaki, Miklos Vecsernyes
• Journal: Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 9 Issue 11 Pg. 1851-61 (Nov 2007) ISSN: 1523-0864 [Print] United States
• PMID: 17715999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenocorticotropic Hormone
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat
• Caspase 3

Topics

• Adrenocorticotropic Hormone (pharmacology, therapeutic use)
• Animals
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Dose-Response Relationship, Drug
• Heart (physiopathology)
• Heart Ventricles (pathology)
• Heme Oxygenase (Decyclizing) (metabolism)
• Immunohistochemistry
• In Situ Nick-End Labeling
• Myocardial Reperfusion Injury (drug therapy, etiology, physiopathology, prevention & control)
• Myocytes, Cardiac (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley