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 truncated analogue [hPAMP(12-20)], and adrenomedullin (hADM) were investigated in the mesenteric vascular bed of the cat. Under constant-flow conditions, injections of hPAMP, hPAMP(12-20), and hADM caused dose-related decreases in mesenteric perfusion pressure. hADM was 100-fold more potent than hPAMP, and 1000-fold more potent than hPAMP(12-20). Vasodilator responses to hPAMP and hADM were not altered by adrenergic-blocking agents, were similar in innervated and denervated preparations, and were similar when tone was increased by sympathetic nerve stimulation or phenylephrine infusion. Vasodilator responses to hPAMP and hADM were increased in duration by rolipram, a cAMP phosphodiesterase inhibitor. 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.