Growth hormone and hexarelin prevent endothelial vasodilator dysfunction in aortic rings of the hypophysectomized rat

The endothelial vasodilation mechanism(s) has been investigated in aortic r ings of hypophysectomized male rats as well as hypophysectomized rats treat ed for 7 days with growth hormone (GH, 400 mu g/kg, s.c.) or hexarelin (80 mu g/kg, s.c.). Tissue preparations from intact animals were taken as contr ols. The results obtained indicate that the release of 6-keto-prostaglandin F-1 alpha (6-keto-PGF(1 alpha)) from aortic rings of hypophysectomized rat s was markedly reduced(51%; p < 0.01) as compared with that of control prep arations; the peak response to cumulative concentration of endothelin-1 (ET -I, from 10(-11) to 10(-5) M) was increased 2.4-fold (p < 0.01) versus cont rols; the relaxant activity of acetylcholine (ACh, from 10(-10) to 10(-4) M ) in norepinephrine-precontracted aortic rings was reduced by 39.5 +/- 4.4% . Pretreatment of hypophysectomized rats with GH or hexarelin markedly anta gonized the hyperresponsiveness of the aortic tissue to ET-I and allowed a consistent recovery of both the relaxant activity of ACh and the generation of 6-keto-PGF(1 alpha). Collectively these findings support the concept th at dysfunction of vascular endothelial cells may be induced by a defective GH function. Because a replacement regimen of GH restored the somatotropic function and increased plasma insulin-like growth factor-I (IGF-I) concentr ations in the hypophysectomized rats, it is suggested that IGF-I may have p rotected the vascular endothelium acting as a biologic mediator of GH actio n. Tn contrast to GH, hexarelin replacement neither increased body weight n or affected the plasma concentrations of IGF-I, indicating that its benefic ial action on vascular endothelium was divorced from that on somatotropic f unction and was likely due to activation of specific endothelial receptors.