Alpha-MSH induces vasodilatation and exerts cardioprotection via the heme-oxygenase pathway in rat hearts

Alpha-melanocyte-stimulating hormone ( α-MSH) is a protein with known capacity for protection against cardiovascular ischemia-reperfus ion (I/R) injury. The present 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 o n the activity of heme oxygenase-1 (HO1, hsp-32), a heat shock protein that functions as a major antioxidant defense molecule. Healthy male Sprague-Dawley rats were used for all experiments. Following treatment with selected doses of α-MSH, echocardiographic examinations were carried o ut n live, anesthetized animals. Hearts were harvested from an esthetized 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 p rotocol. Induction of global ischaemia was performed, followed by during-reperfusion asses ment of cardiac functions. Determination of incidence of cardiac arrhythmias w as made by ECG. Major outcomes include echocardiographic data, suggesting that α-MSH has mild effects on systolic parameters, along with potent antiarrhythmic effect s. Of particular significance was the specificity of dilatative effects on coronary vascu lat re, and similar outcomes of aortic ring experiments, which potentially allow different dose s of the compound to be used to selectively target various portions of the vasculat ure for dilation.