Hexarelin, but not growth hormone, protects heart from damage induced in vitro by calcium deprivation replenishment.
The effects of hexarelin, a growth hormone (GH) secretagogue, and human GH on the mechanical and metabolic changes measured in isolated rat hearts submitted to 5 min of Ca2+ deprivation followed by reperfusion with Ca2+-containing medium, the so-called calcium paradox phenomenon, were studied. Hexarelin (80 microg/kg bid, subcutaneously) administered for 7 d to male rats effectively antagonized the sudden increase in resting tension measured in vitro on Ca2+ repletion. Moreover, during Ca2+ repletion the release of creatine kinase activity (an index of cell damage) in the perfusate of these hearts was reduced up to 40% compared with controls. By contrast, administration of hexarelin for 3 d or GH (400 microg/kg bid, subcutaneously) for 7 d did not affect the mechanical and metabolic alterations induced by the calcium paradox. To assess its direct and acute cardiac effects, hexarelin (8 microg/mL) was perfused in vitro in recirculating conditions for 60 min through the hearts of normal rats. In this case, hexarelin did not stimulate heart contractility and failed to prevent ventricular contracture upon Ca2+ readmission, whereas diltiazem, a Ca2+channel blocker, effectively antagonized the calcium paradox phenomenon. We conclude that short-term in vivo exposure to hexarelin, but not GH, enables cardiac myocyites to prevent cytoplasmatic electrolytic unbalance and to control intracellular Ca2+ gain, two functions largely impaired during the calcium paradox phenomenon. Moreover, because the effect of hexarelin is not acute but dependent on the length of in vivo treatment, we suggest that it requires modifications of myocardiocyte physiology.
Torsello
A
A
Department of Experimental and Environmental Medicine and Biotechnologies, University of Milan-Bicocca, Milan, Italy. antonio.torsello@unimib.it
Rossoni
G
G
Locatelli
V
V
De Gennaro Colonna
V
V
Bernareggi
M
M
Francolini
M
M
Müller
E E
EE
Berti
F
F
D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000172:deficiency / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006728:Hormones / Q000494:pharmacology*; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology*; D009929:Organ Size; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D006728:Hormones; D009842:Oligopeptides; C086184:hexarelin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003402:Creatine Kinase; D002118:Calcium