CENTRAL CARDIOVASCULAR EFFECTS OF JOINING PEPTIDE IN GENETICALLY HYPERTENSIVE RATS

Joining peptide (JP) is one of the major products of proopiomelanocort in (POMC). The biological function of this peptide has not been clarif ied despite its relative abundance in the pituitary and the hypothalam us. Recently we demonstrated that JP, which was isolated from bovine p osterior pituitary, possesses Na pump inhibitor activity. The purpose of this study is to explore the physiological relevance of JP in cardi ovascular regulation. For these investigations, we used the synthetic peptides bovine JP (bJP) and COOH-terminally amidated rat JP (rJP), si nce JP is known to have sequence variability among species. Intraciste rnal administration of both bJP and rJP in urethan-anesthetized rats e voked similar hypertensive and tachycardic effects. The effects of bot h peptides were markedly greater in the spontaneously hypertensive rat s (SHR) compared with the normotensive Wistar Kyoto rats (WKY). Intrav enous bolus injections of rJP at the same doses were without effect. A utoradiography, using I-125-labeled [0Tyr]-rJP as a ligand, revealed s pecific binding sites for rJP in the dorsal medulla in areas correspon ding to the nucleus tractus solitarii (NTS) (extending from approximat ely 0.4 mm caudal to 1.8 mm rostral to the obex). Microinjections of r JP into the caudal part of the NTS of anesthetized SHR produced dose r elated pressor and tachycardic responses. The pressor and tachycardic responses were also observed at the rostral part of the NTS, whereas t he injections into the intermediate part of the NTS evoked depressor a nd bradycardic responses in SHR. These results suggest that at doses t ested, the site of JP action resides in the central nervous system, an d that JP is a potent neuropeptide in medullary sites known to be pivo tal in central cardiovascular regulation. The effect of JP is especial ly prominent in the genetically hypertensive rat.