CENTRAL ACTIONS OF ADRENOMEDULLIN ON CARDIOVASCULAR PARAMETERS AND SYMPATHETIC OUTFLOW IN CONSCIOUS RATS

Adrenomedullin (ADM) is reported to be a peripherally acting hypotensi ve peptide, but its central actions are unclear. We investigated the e ffects of centrally administered ADM on blood pressure (BP), heart rat e (HR), and renal sympathetic nerve activity (RSNA) in conscious rats and sinoaortic-denervated (SAD) rats. We also investigated the recepto rs interacting with ADM using two putative antagonists. Intracerebrove ntricular administration of ADM in doses of 0.1 and 0.5 nmol/kg caused tachycardia and early inhibition of RSNA. Central ADM (1.0 nmol/kg) i nduced hypertension, tachycardia, and a decrease followed by an increa se in RSNA. In SAD rats, increases in BP, HR, and RSNA at the late pha se were enhanced by central ADM (1.0 nmol/kg), whereas the early decre ase in RSNA remained. Thus the inhibition of RSNA via central ADM may be unrelated to the arterial baroreceptor reflex. Pretreatment with an tagonists human calcitonin gene-related peptide-(8-37) and human ADM-( 22-52) significantly suppressed the central actions of ADM. The findin gs suggest that ADM is involved as a neuropeptide in the receptor-medi ated central regulation of the cardiovascular system and RSNA.