CARDIAC ISCHEMIA AND IMPAIRMENT OF VASCULAR ENDOTHELIUM FUNCTION IN HEARTS FROM GROWTH HORMONE-DEFICIENT RATS - PROTECTION BY HEXARELIN

The ability of hexarelin, an effective growth hormone (GH)-releasing h exapeptide, to reverse the worsening of cardiac dysfunction in GH-defi cient animals was studied in young male rats passively immunized by ad ministration of an anti-GH-releasing hormone (GHRH) serum. Heart prepa rations from anti-GHRH serum-treated rats, undergoing low-flow ischemi a and reperfusion, showed: (1) a progressive increase of left ventricu lar end-diastolic pressure during the ischemic period and a poor recov ery of contractility at reperfusion with a consistent decrease of the left ventricular-developed pressure; (2) a decreased rate of formation of 6-keto-prostaglandin F-1 alpha. (6-keto-PGF(1 alpha)), a stable me tabolite of prostacyclin, in perfusates from preischemic and reperfusi on periods; (3) an increased vasopressor activity of angiotensin II. H exarelin (80 mu g/kg, bid, s.c.), administered for 15 days to anti-GHR H serum-treated rats, restored to normal the impaired somatotropic fun ction and counteracted the ischemic damage, improving postischemic lef t ventricular developed pressure to values higher than those of contro ls. Furthermore, both the generation of 6-keto-PGF(1 alpha) and the va sopressor activity of angiotensin II reverted to those of control prep arations. Administration of hexarelin to control rats induced a consid erable improvement of postischemic ventricular function of the perfuse d hearts which was similar to that present in preparations from anti-G HRH serum-treated rats given hexarelin. This protective activity was d ivorced from any further stimulation of somatotropic function. Collect ively, these data indicate that, in GH-deficient rats, hexarelin is ca pable of restoring somatotropic function and has a beneficial effect i n myocardial ischemia and reperfusion damage. In addition, the increas ed responsiveness of the coronary vasculature to angiotensin II and th e decreased generation of prostacyclin in hearts from GH-deficient rat s would indicate that for prevention of injury and dysfunction of the vascular endothelium a normal somatotropic function is mandatory. (C) 1997 Elsevier Science B.V.