Central cardiovascular effects of joining peptide in genetically hypertensive rats

Abstract

Joining peptide (JP) is one of the major products of proopiomelanocortin (POMC). The biological function of this peptide has not been clarified despite its relative abundance in the pituitary and the hypothalamus. Recently we demonstrated that JP, which was isolated from bovine posterior pituitary, possesses Na pump inhibitor activity. The purpose of this study is to explore the physiological relevance of JP in cardiovascular regulation. For these investigations, we used the synthetic peptides bovine JP (bJP) and COOH-terminally amidated rat JP (rJP), since JP is known to have sequence variability among species. Intracisternal administration of both bJP and rJP in urethan-anesthetized rats evoked similar hypertensive and tachycardia effects. The effects of both peptides were markedly greater in the spontaneously hypertensive rats (SHR) compared with the normotensive Wistar Kyoto rats (WKY). Intravenous bolus injections of rJP at the same doses were without effect. Autoradiography, using 125I-labeled [0Tyr]-rJP as a ligand, revealed specific binding sites for rJP in the dorsal medulla in areas corresponding to the nucleus tractus solitarii (NTS) (extending from approximately 0.4 mm caudal to 1.8 mm rostral to the obex). Microinjections of rJP into the caudal part of the NTS of anesthetized SHR produced dose-related pressor and tachycardic responses. The pressor and tachycardic responses were also observed at the rostral part of the NTS, whereas the injections into the intermediate part of the NTS evoked depressor and bradycardic responses in SHR. These results suggest that at doses tested, the site of JP action resides in the central nervous system, and that JP is a potent neuropeptide in medullary sites known to be pivotal in central cardiovascular regulation. The effect of JP is especially prominent in the genetically hypertensive rat.