title: Rat intermedin1-47 does not improve functional recovery in postischemic hearts.
abstract: Intermedin, a novel member of the calcitonin/calcitonin gene-related peptide family identified from vertebrate genomes, may directly affect cardiac function but current studies revealed no clear picture. The aims of our study were to compare direct contractile effects of intermedin on cardiomyocytes to that on the whole organ and to investigate whether intermedin improves postischemic recovery independent of an effect on acute reperfusion injury. Isolated adult rat ventricular cardiomyocytes were electrically paced and cell shortening was monitored as a readout associated to cardiac performance. Calcium transients were analyzed by Fura-2AM loading of these cells. Isolated rat hearts were investigated by Langendorff perfusion under nonischemic conditions and after 45-min no-flow ischemia followed up by 30-min reperfusion prior to drug testing. Intermedin caused a positive contractile effect on cardiomyocytes that was mediated by protein kinase A activation and accompanied by improved calcium transients. In contrast, intermedin reduced left ventricular developed pressure in Langendorff-perfused rat hearts. This negative inotropic effect was attenuated by inhibition of nitric oxide synthesis. In postischemic hearts (impaired nitric oxide synthesis), the negative inotropic effect was attenuated but no positive inotropic effect occurred. However, intermedin caused robust vasodilation in nonischemic and postischemic hearts. Our findings suggest that the peptide binds preferentially to vascular cells in the intact organ. The loss of nitric oxide induction in postischemic hearts attenuates a negative inotropic effect of intermedin but does not improve cardiac performance independent of acute reperfusion injury.
authors: Physiologisches Institut, Justus-Liebig-Universität, Aulweg 149, 35392, Giessen, Germany.
authors: Gerald
authors: G
authors: Münzel
authors: Alexander
authors: A
authors: Schlier
authors: Rolf
authors: R
authors: Schreckenberg
authors: Yaser
authors: Y
authors: Abdallah
authors: Klaus-Dieter
authors: KD
authors: Schlüter
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
chemical_list: C499411:Adm2 protein, rat; D009479:Neuropeptides; D053607:Adrenomedullin; D009569:Nitric Oxide; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium