PROADRENOMEDULLIN NH2-TERMINAL-20 PEPTIDE HAS CAMP-MEDIATED VASODILATOR ACTIVITY IN THE MESENTERIC VASCULAR BED OF THE CAT

Responses to proadrenomedullin NH2-terminal 20 peptide (hPAMP), a trun cated analogue [hPAMP(12-20)], and adrenomedullin (hADM) were investig ated in the mesenteric vascular bed of the cat. Under constant-flow co nditions, injections of hPAMP, hPAMP(12-20), and hADM caused dose-rela ted decreases in mesenteric perfusion pressure. hADM was 100-fold more potent than hPAMP, and 1000-fold more potent than hPAMP(12-20). Vasod ilator responses to hPAMP and hADM were not altered by adrenergic-bloc king agents, were similar in innervated and denervated preparations, a nd were similar when tone was increased by sympathetic nerve stimulati on or phenylephrine infusion. Vasodilator responses to hPAMP and hADM were increased in duration by rolipram, a cAMP phosphodiesterase inhib itor. The present data suggest that vasodilator responses to the hPAMP and hADM are mediated by an increase in cAMP and that an interaction with the adrenergic nervous system is not involved. Copyright (C) 1996 Elsevier Science Inc.