Ghrelin plays a minor role in the physiological control of cardiac function in the rat.
We have previously reported that a 7-d pretreatment with hexarelin, a synthetic ligand of the GH secretagogue receptor (GHS-R), largely prevented damages induced by ischemia and reperfusion in isolated rat hearts. Our aim was to ascertain whether ghrelin, an endogenous ligand of the GHS-R, is physiologically endowed with cardioprotective activity. Hypophysectomized rats were treated in vivo for 7 d with either ghrelin (320 microg/kg) or hexarelin (80 microg/kg), and their hearts were subjected in vitro to the ischemia and reperfusion procedure. Ghrelin was far less effective than hexarelin in preventing increases in left ventricular end-diastolic pressure (15% and 60% protection for ghrelin and hexarelin, respectively), coronary perfusion pressure (10% and 45% reduction), and release of creatine kinase in the heart perfusate (15% and 55% reduction). In the second experiment, normal rats were passively immunized against ghrelin for 21 d before the ischemia and reperfusion procedure. In these isolated hearts, the ischemia-reperfusion damage was not significantly increased compared with control rats. After hypophysectomy, CD36 mRNA levels significantly increased, whereas those of atrial natriuretic factor significantly decreased. We conclude that: 1) ghrelin plays a minor role in the control of heart function; and 2) hexarelin effects are mediated in part by the GHS-R and largely by interactions with the CD36.
Torsello
Antonio
A
Department of Experimental and Environmental Medicine and Biotechnology, University of Milano-Bicocca, 20052 Monza, Italy. antonio.torsello@unimib.it
Bresciani
Elena
E
Rossoni
Giuseppe
G
Avallone
Roberta
R
Tulipano
Giovanni
G
Cocchi
Daniela
D
Bulgarelli
Ilaria
I
Deghenghi
Romano
R
Berti
Ferruccio
F
Locatelli
Vittorio
V
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D018955:CD36 Antigens / Q000235:genetics; D002316:Cardiotonic Agents / Q000494:pharmacology; D054439:Ghrelin; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D007016:Hypophysectomy; D007116:Immunization, Passive; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D036361:Peptide Hormones / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
D018955:CD36 Antigens; D002316:Cardiotonic Agents; D054439:Ghrelin; D009842:Oligopeptides; D036361:Peptide Hormones; D012333:RNA, Messenger; C086184:hexarelin; D009320:Atrial Natriuretic Factor