The present investigation evaluates the cardiovascular effects of the anorexigenic mediator\nalpha-melanocyte stimulating hormone (MSH), in a rat model of type 2 diabetes. Osmotic mini pumps\ndelivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF)\nrats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose\ntolerance (OGTT). Echocardiography was conducted and, following sacrifice, the effects of treatment\non ischemia/reperfusion cardiac injury were assessed using the isolated working heart method.\nNicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was measured to evaluate\nlevels of oxidative stress, and force measurements were performed on isolated cardiomyocytes to\ndetermine calcium sensitivity, active tension and myofilament co-operation. Vascular status was also\nevaluated on isolated arterioles using a contractile force measurement setup. The echocardiographic\nparameters ejection fraction (EF), fractional shortening (FS), isovolumetric relaxation time (IVRT),\nmitral annular plane systolic excursion (MAPSE), and Tei-index were significantly better in the\nMSH-treated group compared to ZDF controls. Isolated working heart aortic and coronary flow was\nincreased in treated rats, and higher Hill coefficient indicated better myofilament co-operation in the\nMSH-treated group. We conclude that MSH improves global heart functions in ZDF rats, but these\neffects are not related to the vascular status.
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