Positive inotropy of calcitonin gene-related peptide and amylin on porcineisolated myocardium

Isolated porcine myocardial trabeculae from right atria and left ventricles were paced at 1.5 Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. Alpha calcitonin gene-related peptide (alpha-CGRP) increased contractile force in nearly half of the tra beculae, whereas the selective CGRP(2) receptor agonist [Cys(acetylmethoxy) (2,7)]-CGRP had effect in only a few. Preincubation with the CGRP(1) recept or antagonist alpha-CGRP-(8-37) (10(-6) M) almost completely blocked positi ve inotropic responses to alpha-CGRP. Amylin had weak positive inotropic ef fects in some atrial, but not in ventricular trabeculae. Adrenomedullin did not affect contractility in either atrial or ventricular trabeculae. In co nclusion, these results suggest that alpha-CGRP has a positive inotropic ef fect that can be mediated by both CGRP(1) and CGRP(2) receptors. Amylin see ms to have a potential positive inotropic effect on atrial tissue, whereas no direct effect of adrenomedullin could be measured. (C) 1999 Elsevier Sci ence B.V. All rights reserved.