title: Alpha-Melanocyte-stimulating Hormone Induces Vasodilation and Exerts Cardioprotection Through the Heme-Oxygenase Pathway in Rat Hearts.
abstract: Alpha-melanocyte-stimulating hormone (α-MSH) is a protein with known capacity for protection against cardiovascular ischemia-reperfusion (I/R) injury. This investigation evaluates the capacity of α-MSH to mitigate I/R effects in an isolated working rat heart model and determine the dependency of these alterations on the activity of heme oxygenase-1 (HO-1, hsp-32), a heat shock protein that functions as a major antioxidant defense molecule. Healthy male Sprague Dawley rats were used for all experiments. After treatment with selected doses of α-MSH, echocardiographic examinations were performed on live, anesthetized animals. Hearts were harvested from anesthetized rats pretreated with α-MSH and/or the HO-1 inhibitor SnPP, followed by cardiac function assessment on isolated working hearts, which were prepared using the Langendorff protocol. Induction of global ischemia was performed, followed by during reperfusion assessment of cardiac functions. Determination of incidence of cardiac arrhythmias was made by electrocardiogram. Major outcomes include echocardiographic data, suggesting that α-MSH has mild effects on systolic parameters, along with potent antiarrhythmic effects. Of particular significance was the specificity of dilatative effects on coronary vasculature, and similar outcomes of aortic ring experiments, which potentially allow different doses of the compound to be used to selectively target various portions of the vasculature for dilation.
authors.affiliation: *Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary; †Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; ‡Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary; §Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; and ¶Department of Cardiology, Faculty of Medicine, Division of Clinical Physiology, University of Debrecen, Debrecen, Hungary.
authors.forename: Miklos
authors.initials: M
authors.lastname: Vecsernyes
authors.forename: Miklos
authors.initials: M
authors.lastname: Szokol
authors.forename: Mariann
authors.initials: M
authors.lastname: Bombicz
authors.forename: Daniel
authors.initials: D
authors.lastname: Priksz
authors.forename: Rudolf
authors.initials: R
authors.lastname: Gesztelyi
authors.forename: Gabor Aron
authors.initials: GA
authors.lastname: Fulop
authors.forename: Balazs
authors.initials: B
authors.lastname: Varga
authors.forename: Bela
authors.initials: B
authors.lastname: Juhasz
authors.forename: David
authors.initials: D
authors.lastname: Haines
authors.forename: Arpad
authors.initials: A
authors.lastname: Tosaki
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000067268:Isolated Heart Preparation; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D011524:Protoporphyrins / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; D014665:Vasodilator Agents; D000521:alpha-MSH; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat