Hexarelin, a growth hormone secretagogue, protects the isolated rat heart from ventricular dysfunction produced by exposure to calcium-free medium

Citation
G. Rossoni et al., Hexarelin, a growth hormone secretagogue, protects the isolated rat heart from ventricular dysfunction produced by exposure to calcium-free medium, PHARMAC RES, 42(2), 2000, pp. 129-136
Citations number
22
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACOLOGICAL RESEARCH
ISSN journal
10436618 → ACNP
Volume
42
Issue
2
Year of publication
2000
Pages
129 - 136
Database
ISI
SICI code
1043-6618(200008)42:2<129:HAGHSP>2.0.ZU;2-0
Abstract
The effect of hexarelin, a potent synthetic growth hormone (GH)-secretagogu e, and of human GH were studied on the mechanical and metabolic changes eli cited by the calcium-paradox phenomenon in isolated rat hearts submitted to 5 min Ca2+-depletion followed by reperfusion with reintegrated Ca2+ medium . Hexarelin, (80 mu g kg(-1) s.c.) administered to normal male young rats f or 3 and 7-day, time-dependently antagonized the sudden increase in resting tension of the isolated perfused hearts upon Ca2+-repletion. The beneficia l effect of hexarelin was particularly evident in the 7-day treatment. In t his 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 efflue nt during Ca2+-repletion was reduced by 40% (P < 0.001) as compared to cont rols. The protecting activity of hexarelin against the damage induced by ca lcium-paradox in the heart was apparently divorced from any stimulation of the GH/insulin-like growth factor (IGF) axis, since plasma and heart concen trations of IGF-1 were similar to those measured in control rats. In contra st to hexarelin, administration of GH (400 mu g 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 mu g ml(-1)) perfused for 60 min through the hearts in recircu lating conditions did not modify heart contractility and failed to prevent ventricular hypercontractility developed on Ca2+ 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, t hat only prolonged exposure to hexarelin makes myocardial cells competent t o maintain cytoplasmatic electrolyte balance and to control of Ca2+ gain, t wo functions that are impaired during the 'calcium-paradox' phenomenon. (C) 2000 Academic Press.