title: Hexarelin, a growth hormone secretagogue, protects the isolated rat heart from ventricular dysfunction produced by exposure to calcium-free medium.
abstract: The effect of hexarelin, a potent synthetic growth hormone (GH)-secretagogue, and of human GH were studied on the mechanical and metabolic changes elicited by the calcium-paradox phenomenon in isolated rat hearts submitted to 5 min Ca(2+)-depletion followed by reperfusion with reintegrated Ca(2+)medium. Hexarelin, (80 microg kg(-1)s.c.) administered to normal male young rats for 3 and 7-day, time-dependently antagonized the sudden increase in resting tension of the isolated perfused hearts upon Ca(2+)-repletion. The beneficial effect of hexarelin was particularly evident in the 7-day treatment. In this instance, ventricular contraction peaked at 30 +/- 2 mmHg (controls, 76 +/- 7 mmHg) and the recovery of left ventricular developed pressure (LVDP) was two times higher (P<0.001) than that recorded in controls (LVDP, 29 +/- 2 mmHg). Moreover, the release of creatine kinase into the heart effluent during Ca(2+)-repletion was reduced by 40% (P<0.001) as compared to controls. The protecting activity of hexarelin against the damage induced by calcium-paradox in the heart was apparently divorced from any stimulation of the GH/insulin-like growth factor (IGF) axis, since plasma and heart concentrations of IGF-1 were similar to those measured in control rats. In contrast to hexarelin, administration of GH (400 microg kg(-1) s.c.) for 7 days did not affect the mechanical and metabolic manifestations of calcium-paradox in the perfused rat hearts. Hexarelin (8 microg ml(-1)) perfused for 60 min through the hearts in recirculating conditions did not modify heart contractility and failed to prevent ventricular hypercontractility developed on Ca(2+)-readmission. In conclusion, the mode of action of hexarelin in protecting the rat heart from calcium-paradox events is presently unknown; it would seem, however, that only prolonged exposure to hexarelin makes myocardial cells competent to maintain cytoplasmatic electrolyte balance and to control of Ca(2+)gain, two functions that are impaired during the 'calcium-paradox' phenomenon.
authors.affiliation: Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Via Vanvitelli 32, Milan, 20129, Italy. giuseppe.rossoni@unimi.it
authors.forename: G
authors.initials: G
authors.lastname: Rossoni
authors.forename: V
authors.initials: V
authors.lastname: Locatelli
authors.lastname: Gennaro Colonna Vd
authors.forename: E E
authors.initials: EE
authors.lastname: Müller
authors.forename: F
authors.initials: F
authors.lastname: Berti
mesh_terms: D000818:Animals; D002118:Calcium / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D003470:Culture Media; D006133:Growth Substances / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D019382:Human Growth Hormone / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D003470:Culture Media; D006133:Growth Substances; D009842:Oligopeptides; C086184:hexarelin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D003402:Creatine Kinase; D002118:Calcium