Positive inotropic effects of adrenomedullin on rat papillary muscle.
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.
Ihara
T
T
Department of Cardiology, Jichi Medical School, Minamikawachi-Machi, Tochigi, Japan.
Ikeda
U
U
Tate
Y
Y
Ishibashi
S
S
Shimada
K
K
D053607:Adrenomedullin; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D010446:Peptide Fragments; D010455:Peptides; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide