We previously reported that induction of selective GH deficiency in the rat exacerbates cardiac dysfunction induced by experimental
ischemia and reperfusion performed on the explanted heart. In the same model, short-term treatment with
hexarelin, a GH-releasing
peptide, reverted this effect, as did GH. To ascertain whether
hexarelin had non-GH-mediated protective effects on the heart, we compared
hexarelin and GH treatment in hypophysectomized rats.
Hexarelin (80 microg/kg sc), given for 7 days, prevented exacerbation of the
ischemia-
reperfusion damage induced by
hypophysectomy. We also demonstrate that
hexarelin prevents increases in left ventricular end diastolic pressure, 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 microg/kg sc) produced similar results, whereas administration of
EP 51389 (80 microg/kg sc), another GH-releasing
peptide that does not bind to the heart, was ineffective. In conclusion, we demonstrate that
hexarelin prevents cardiac damage after
ischemia-reperfusion, and that its action is not mediated by GH but likely occurs through activation of specific cardiac receptors.