caa a22 4500 477119972 CHVBK 20180405111634.0 cr unu---uuuuu 170330e19960401xx s 000 0 eng 10.1007/BF00227893 doi (NATIONALLICENCE)springer-10.1007/BF00227893 Mechanical effects of ET-1 in cardiomyocytes isolated from normal and heart-failed rabbits [Elektronische Daten] [Elizabeth Kelso, Robert Geraghty, Barbara McDermott, Elisabeth Trimble, D. Nicholls, Bernard Silke] Endothelin (ET-1) is found at elevated concentrations in the plasma of patients with heart failure and in animal models of cardiomyopathy. The peptide is a potent positive inotropic agent, the effects of which are mediated by increases in cytosolic Ca2+ in cardiomyocytes. The object of this study was to investigate at the cellular level, the actions of ET-1 on contractile function and on Ca2+ currents in heart-failed ventricular myocardium. Male New Zealand White rabbits (8 wks) were treated with twice weekly injections of epirubicin (4 mg/kg/wk, n=7) or with saline (n=7) for 6 wks, followed by a washout period of 2 wks. Ventricular cardiomyocytes were isolated from rabbit hearts using Langendorff perfusion with collagenase; contractile function was examined using a video microscopy method, and L-type Ca2+ currents were recorded using a whole-cell patch-clamp technique. ET-1 produced a concentration-dependent increase in contractile response (% increase from basal value) to a maximum at 1 nM ET-1 of 69 ± 11% (mean ± S.D.) in control cardiomyocytes and 33 ± 6% in heart-failed cells. However, there was no significant change in the EC50 obtained with ET-1 for healthy (0.31 ± 0.1 nM) and for failed cardiomyocytes (0.24 ± 0.1 nM). The effects of ET-1 on L-type Ca2+ channels were similar with a peak amplitude at 1 nM ET-1 of −3.26 ± 0.8 ⋬ in control cardiomyocytes and −3.32 ± 0.9 nA in heart-failed cells. The attenuation of the contractile response to ET-1 in heart-failed cells may reflect a desensitization of ET receptors as a consequence of elevated circulating levels of ET and was not reflected by alteration of transmembrane Ca2+ conductance. It is probable, therefore, that multiple signalling pathways are involved in the actions of ET on ventricular myocardium. Kluwer Academic Publishers, 1996 endothelin-1 nationallicence ventricular cardiomyocytes nationallicence contraction nationallicence calcium nationallicence heart failure nationallicence Kelso Elizabeth Department of Therapeutics and Pharmacology, The Queen's University, Belfast, Northern Ireland aut Geraghty Robert Department of Therapeutics and Pharmacology, The Queen's University, Belfast, Northern Ireland aut McDermott Barbara Department of Therapeutics and Pharmacology, The Queen's University, Belfast, Northern Ireland aut Trimble Elisabeth Department of Clinical Biochemistry, The Queen's University, Belfast, Northern Ireland aut Nicholls D. The Royal Victoria Hospital, Belfast, Northern Ireland aut Silke Bernard Department of Therapeutics and Pharmacology, The Queen's University, Belfast, Northern Ireland aut Molecular and Cellular Biochemistry Kluwer Academic Publishers 157/1-2(1996-04-01), 149-155 0300-8177 157:1-2<149 1996 157 11010 https://doi.org/10.1007/BF00227893 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00227893 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kelso Elizabeth Department of Therapeutics and Pharmacology, The Queen's University, Belfast, Northern Ireland aut NATIONALLICENCE 700 1- Geraghty Robert Department of Therapeutics and Pharmacology, The Queen's University, Belfast, Northern Ireland aut NATIONALLICENCE 700 1- McDermott Barbara Department of Therapeutics and Pharmacology, The Queen's University, Belfast, Northern Ireland aut NATIONALLICENCE 700 1- Trimble Elisabeth Department of Clinical Biochemistry, The Queen's University, Belfast, Northern Ireland aut NATIONALLICENCE 700 1- Nicholls D. The Royal Victoria Hospital, Belfast, Northern Ireland aut NATIONALLICENCE 700 1- Silke Bernard Department of Therapeutics and Pharmacology, The Queen's University, Belfast, Northern Ireland aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Kluwer Academic Publishers 157/1-2(1996-04-01), 149-155 0300-8177 157:1-2<149 1996 157 11010 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer