Growth hormone-independent cardioprotective effects of hexarelin in the rat

We previously reported that induction of selective GH deficiency in the rat exacerbates cardiac dysfunction induced by experimental ischemia and reper fusion performed on the explanted heart. In the same model, short-term trea tment with hexarelin, a GH-releasing peptide, reverted this effect, as did GH. To ascertain whether hexarelin had non-GH-mediated protective effects o n the heart, are compared hexarelin and GH treatment in hypophysectomized r ats. Hexarelin (80 mu g/kg sc), given for 7 days, prevented exacerbation of the ischemia-reperfusion damage induced by hypophysectomy. we also demonst rate that hexarelin prevents increases in left ventricular end diastolic pr essure, coronary perfusion pressure, reactivity of the coronary vasculature to angiotensin II, and release of creatine kinase in the heart perfusate. Moreover, hexarelin prevents the fall in prostacyclin release and enhances recovery of contractility. Treatment with GH (400 mu g/kg sc) produced simi lar results, whereas administration of EP 51389 (80 mu g/kg sc), another GH -releasing peptide that does not bind to the heart, was ineffective. In con clusion, we demonstrate that hexarelin prevents cardiac damage after ischem ia-reperfusion, and that its action is not mediated by GH but likely occurs through activation of specific cardiac receptors.