KP-102 (growth hormone-releasing peptide-2) attenuates ischemia/reperfusion injury in isolated rat hearts.
KP-102, a synthetic growth hormone (GH)-releasing peptide, exerts a variety of effects on cardiac function. In the present study, we investigated the direct cardiac effects of KP-102 with regard to ischemia/reperfusion injury by using isolated rat hearts. Isolated Wistar rat hearts were mounted on a Langendorff apparatus and subjected to 30 min of ischemia followed by 40 min of reperfusion. The rat hearts were treated with 0.1-10 nmol/l KP-102 beginning from 15 min before ischemia until the end of the experiment, with the exception of the ischemia period. Cardiac parameters such as the left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), maximum dP/dt (+dP/dtmax), minimum dP/dt (-dP/dtmax), and heart rate (HR) were measured. The following ischemia/reperfusion-induced cardiac dysfunctions were observed: increased LVEDP and decreased LVDP, +dP/dtmax, and -dP/dtmax. KP-102 at a dose of 0.1 nmol/l or more induced lower LVEDP and higher LVDP and gave higher +dP/dtmax and -dP/dtmax values during the reperfusion as compared with the control groups. In particular, KP-102 at 10 nmol/l clearly suppressed the increase in the LVEDP after reperfusion; eventually, the LVEDP was restored to the preischemia level. At 40 min of reperfusion, 10 nmol/l KP-102 noticeably increased the LVDP, +dP/dtmax, and -dP/dtmax, as compared with the control. KP-102 had no effect on the HR throughout the experiment. In conclusion, KP-102 improved cardiac function in rat isolated hearts subjected to ischemia/reperfusion injury, which is independent of GH secretion.
Furuta
Sadayoshi
S
Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd, 14, Shinomiya, Kyoto 607-8042, Japan. furuta_sadayoshi@kaken.co.jp
Hori
Toshimitsu
T
Ohyama
Tadashi
T
D000818:Animals; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects
D009842:Oligopeptides; C091874:growth hormone-releasing peptide-2