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KP-102 (growth hormone-releasing peptide-2) attenuates ischemia/reperfusion injury in isolated rat hearts

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Abstract

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.

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Authors and Affiliations

  1. Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd, 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto, 607-8042, Japan

    Sadayoshi Furuta, Toshimitsu Hori & Tadashi Ohyama

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  1. Sadayoshi Furuta
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  2. Toshimitsu Hori
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  3. Tadashi Ohyama
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Correspondence to Sadayoshi Furuta.

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Furuta, S., Hori, T. & Ohyama, T. KP-102 (growth hormone-releasing peptide-2) attenuates ischemia/reperfusion injury in isolated rat hearts. Naunyn-Schmied Arch Pharmacol 373, 360–366 (2006). https://doi.org/10.1007/s00210-006-0079-9

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