Abstract:
:Adrenomedullin is a peptide recently isolated from pheochromocytoma that has vasorelaxant and long-lasting hypotensive activities. Plasma levels of adrenomedullin are elevated in patients with congestive heart failure, but the effects of adrenomedullin on the cardiac function are unclear. We, thus, investigated the effects of adrenomedullin on the contraction of rat papillary muscles. We measured the isometric tension and cAMP contents of isolated rat papillary muscles. Adrenomedullin exhibited concentration-dependent inotropic effects. Adrenomedullin also significantly increased intracellular contents of cAMP. Addition of the calcitonin gene-related peptide (CGRP) receptor antagonist inhibited both contractile force and cAMP generation of papillary muscles stimulated by adrenomedullin. The adrenomedullin-induced inotropic effect was further increased in the presence of the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), while the effect was significantly suppressed by KT5720 and Rp-8-bromoadenosine-3',5'-cyclic monophosphorothioate (Rp-8-Br-cAMPS), protein kinase A inhibitors. These results indicate that adrenomedullin has positive inotropic effects on the heart, at least partially through a cAMP-dependent pathway.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Ihara T,Ikeda U,Tate Y,Ishibashi S,Shimada Kdoi
10.1016/s0014-2999(00)00011-xkeywords:
subject
Has Abstractpub_date
2000-02-25 00:00:00pages
167-72issue
1-2eissn
0014-2999issn
1879-0712pii
S0014-2999(00)00011-Xjournal_volume
390pub_type
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