Adrenocorticotrope hormone fragment (4-10) attenuates the ischemia/reperfusion-induced cardiac injury in isolated rat hearts.
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.
Juhasz
Bela
B
Department of Pharmacology, Health Science Center, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary.
Der
Peter
P
Szodoray
Peter
P
Gesztelyi
Rudolf
R
Lekli
Istvan
I
Bak
Istvan
I
Antal
Miklos
M
Maulik
Nilanjana
N
Tosaki
Arpad
A
Vecsernyes
Miklos
M
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000324:Adrenocorticotropic Hormone; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D053148:Caspase 3