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 mes...

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Bibliographic Details
Published in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 1996, Vol.17 (8), p.1379-1387
Main Authors: Champion, H C, Erickson, 3rd, C C, Simoneaux, M L, Bivalacqua, T J, Murphy, W A, Coy, D H, Kadowitz, P J
Format: Article
Language:English
Subjects:
Adamantane - analogs & derivatives
Adamantane - pharmacology
Adrenomedullin
Animals
Cats
Cyclic AMP - physiology
Denervation
Enzyme Inhibitors - pharmacology
Female
Male
Mesenteric Artery, Superior - drug effects
Mesenteric Artery, Superior - innervation
Mesenteric Artery, Superior - physiology
Morpholines - pharmacology
NG-Nitroarginine Methyl Ester - pharmacology
Peptide Fragments - pharmacology
Peptide Fragments - physiology
Peptides - pharmacology
Peptides - physiology
Phentolamine - pharmacology
Proteins - pharmacology
Proteins - physiology
Purinones - pharmacology
Pyrrolidinones - pharmacology
Reserpine - pharmacology
Rolipram
Sympathetic Nervous System - physiology
Sympatholytics - pharmacology
Vasodilation - drug effects
Vasodilation - physiology
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Summary: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.
ISSN:0196-9781
DOI:10.1016/S0196-9781(96)00240-9