Alpha–Melanocyte-stimulating Hormone Induces Vasodilation and Exerts Cardioprotection Through the Heme-Oxygenase Pathway in Rat Hearts

Abstract

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.

Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function in Zucker Diabetic Fatty Rats

“…Moreover, post-ischemic CO and SV values in animals receiving the hormone did not reach statistical significance in magnitude of suppression, versus their pre-ischemic state. These findings are consistent with previous studies by the authors, in which alpha-MSH treatment significantly inhibited the extent of ischemia/reperfusion-induced infarct zones, increased the magnitude of CO and SV, therefore provides additional evidence of the range of cardio-protective effects mediated by the hormone [ 46 ]. These outcomes notwithstanding, little investigative work has addressed this issue at the time of the present writing and awaits further exploration.…”

“…Echocardiographic outcomes shown in Table 2 , reveal the protective effects of long-term alpha-MSH treatment on cardiovascular systolic and diastolic function. This result is relevant to previous work by authors of the present report, in which echocardiographic parameters were monitored using single acute administration of alpha-MSH doses (10, 100 and 250 μg/kg), with resulting significant enhancement of systolic function (EF, FS) [ 46 ]. In the present study, the chronic alpha-MSH treatment engendered a similar pattern.…”

“…Previous investigations have shown that typically alpha-MSH does not affect blood pressure or may only slightly elevate it [ 34 , 46 ]. Moreover, other effects of the hormone on other echocardiographic outcomes shown here, bear consideration.…”

A Novel Therapeutic Approach in the Treatment of Pulmonary Arterial Hypertension: Allium ursinum Liophylisate Alleviates Symptoms Comparably to Sildenafil

“…Isolated working heart is a widespread and well-known method for studying cardiac functions without the innervation of autonomic nervous system [ 38 , 39 ], and our workgroup carried out many experiments based on this method [ 29 , 40 , 41 ]. Echocardiographic and isolated heart data are often well-correlated in many cardiac parameters, however, discrepancies can also be observed, due to the lack of innervation and vegetative and adaptive reflexes in isolated working heart procedures.…”

Peer Review #2 of "Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone (v0.1)"

“…The anti-inflammatory action of α-MSH was proven in animal models of systemic or local inflammation, like sepsis, arthritis, uveitis, dermatitis, pancreatitis and colitis (Brzoska et al, 2008). The protective effect of α-MSH was also shown in ischemic conditions in the heart (Vecsernyés et al, 2003;Vecsernyés et al, 2017), retina (Varga et al, 2013), kidney and intestine (Brzoska et al, 2008). In addition to animal models of gut inflammation (Rajora et al, 1997a), the effects of α-MSH were examined on cell cultures.…”