CATECHOLAMINE RELEASE MEDIATES PRESSOR EFFECTS OF ADRERMOMEDULLIN-(15-22) IN THE RAT

Human adrenomedullin, a novel hypotensive peptide, contains a six-memb er ring structure similar to that found in calcitonin gene-related pep tide and pancreatic amylin. Unlike the full-sequence peptide, human ad renomedullin-(15-22) [hADM-(15-22)], which contains the ring structure : increases systemic arterial pressure in the rat but not the cat. We undertook the present study to investigate the mechanism by which hADM -(15-22) increases systemic arterial pressure in the rat. Injection of hADM-(15-22) in doses of 10 to 300 nmol/kg N increased systemic aaeri al pressure in a dose-dependent manner and was threefold less potent t han norepinephrine when doses were compared on a nanomole basis. Howev er, the ring structures of human calcitonin gene-related peptide and h uman amylin, human calcitonin gene-related peptide-(1-8) and human amy lin-(1-8), respectively, had no significant effect on systemic arteria l pressure in the rat. Presser responses to hADM-(15-22) were reduced significandy after administration of phentolamine or reserpine. Respon ses to hADM-(15-22) were not altered by the angiotensin type 1 blockin g agent DuP 753 or the endothelin-A/endothelin-B receptor blocking age nt bosentan, and responses to hADM-(15-22) and the nicotinic agonist 1 ,1-dimethyl-4-phenylpiperazinium (DMPP) were reduced after bilateral a drenalectomy. Presser responses to DMPP were reduced by hexamethonium, whereas the nicotinic blocking agent had no effect on the presser res ponse to hADM-(15-22). These data suggest that increases in systemic a rterial pressure in response to hADM-(15-22) in the rat are mediated b y the activation of a-adrenergic receptors by catecholamines released from the adrenal medulla. The present data suggest that hADM-(15-22) r eleases catecholamines from the adrenal medulla by a noncholinergic me chanism.