title: Growth hormone and hexarelin prevent endothelial vasodilator dysfunction in aortic rings of the hypophysectomized rat.
abstract: The endothelial vasodilation mechanism(s) has been investigated in aortic rings of hypophysectomized male rats as well as hypophysectomized rats treated for 7 days with growth hormone (GH, 400 microg/kg, s.c.) or hexarelin (80 microg/kg, s.c.). Tissue preparations from intact animals were taken as controls. The results obtained indicate that the release of 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) from aortic rings of hypophysectomized rats was markedly reduced (51%; p<0.01) as compared with that of control preparations; the peak response to cumulative concentration of endothelin-1 (ET-1, from 10(-11) to 10(-5) M) was increased 2.4-fold (p<0.01) versus controls; 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 antagonized the hyperresponsiveness of the aortic tissue to ET-1 and allowed a consistent recovery of both the relaxant activity of ACh and the generation of 6-keto-PGF1alpha. Collectively these findings support the concept that 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) concentrations in the hypophysectomized rats, it is suggested that IGF-I may have protected the vascular endothelium acting as a biologic mediator of GH action. In contrast to GH, hexarelin replacement neither increased body weight nor affected the plasma concentrations of IGF-I, indicating that its beneficial action on vascular endothelium was divorced from that on somatotropic function and was likely due to activation of specific endothelial receptors.
authors.affiliation: Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy. giuseppe.rossoni@unimi.it
authors.forename: G
authors.initials: G
authors.lastname: Rossoni
authors.forename: V
authors.initials: V
authors.lastname: Locatelli
authors.forename: V
authors.initials: V
authors.lastname: De Gennaro Colonna
authors.forename: A
authors.initials: A
authors.lastname: Torsello
authors.forename: F
authors.initials: F
authors.lastname: Schweiger
authors.forename: M
authors.initials: M
authors.lastname: Boghen
authors.forename: M
authors.initials: M
authors.lastname: Nilsson
authors.forename: M
authors.initials: M
authors.lastname: Bernareggi
authors.forename: E E
authors.initials: EE
authors.lastname: Müller
authors.forename: F
authors.initials: F
authors.lastname: Berti
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001011:Aorta; D001835:Body Weight; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007016:Hypophysectomy; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000601:surgery; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D020011:Protective Agents; C086184:hexarelin; D019382:Human Growth Hormone; D019323:omega-N-Methylarginine; D015121:6-Ketoprostaglandin F1 alpha; D000109:Acetylcholine