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This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 101/3/778    most recent 01631.2005v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Dong, F. Articles by Ren, J. Search for Related Content PubMed PubMed Citation Articles by Dong, F. Articles by Ren, J.

Intermedin (adrenomedullin-2) enhances cardiac contractile function via a protein kinase C- and protein kinase A-dependent pathway in murine ventricular myocytes

¹Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming; and ²Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri

Submitted 28 December 2005 ; accepted in final form 25 May 2006

Intermedin (IMD), also called adrenomedullin-2, is a 47-amino acid peptide from the calcitonin gene-related peptide (CGRP)/adrenomedullin family of peptides. Recent studies suggest that IMD may participate in the regulation of cardiovascular function and fluid and electrolyte homeostasis. To evaluate the role of IMD on cardiomyocyte contractile function, electrically paced murine ventricular myocytes were acutely exposed to IMD, and the following indexes were determined: peak shortening (PS), time to PS, time-to-90% relengthening, and maximal velocity of shortening and relengthening. Intracellular Ca²⁺ was assessed using fura 2-AM fluorescent microscopy. Our results revealed that IMD (10 pM to 10 nM) significantly increased PS and maximal velocity of shortening and relengthening in ventricular myocytes, the maximal effect of which (46%) was somewhat comparable to those elicited by CGRP (1 nM) and adrenomedullin (100 nM). Exposure of IMD significantly shortened time-to-90% relengthening without affecting time to PS, similar to CGRP and adrenomedullin. IMD also enhanced intracellular Ca²⁺ release, with a maximal increase of 50%, and facilitated the intracellular Ca²⁺ decay rate. The IMD-induced effects were abolished by the protein kinase C inhibitor chelerythrine (1 µM), downregulation of protein kinase C using phorbol 12-myristate 13-acetate (1 µM), and the protein kinase A inhibitor H89 (1 µM). Our data suggest that IMD acutely augments cardiomyocyte contractile function through, at least in part, a protein kinase C- and protein kinase A-dependent mechanism.

cardiac myocyte; shortening; relengthening