Cardiostimulant effects of urotensin-II in human heart in vitro.
The effects of the recently identified human peptide urotensin-II (hU-II) were investigated on human cardiac muscle contractility and coronary artery tone. In right atrial trabeculae from non-failing hearts, hU-II caused a concentration-dependent increase in contractile force (pEC(50)=9.5+/-0.1; E(max)=31.3+/-4.8% compared to 9.25 mM Ca(2+); n=9) with no change in contraction duration. In right ventricular trabeculae from explanted hearts, 20 nM hU-II caused a small increase in contractile force (7.8+/-1.4% compared to 9.25 mM Ca(2+); n=3/6 tissues from 2 out of 4 patients). The peptide caused arrhythmic contractions in 3/26 right atrial trabeculae from 3/9 patients in an experimental model of arrhythmia and therefore has less potential to cause arrhythmias than ET-1. hU-II (20 nM) increased tone (17.9% of the response to 90 mM KCI) in 7/7 tissues from 1 patient, with no response detected in 8/8 tissues from 2 patients. hU-II is a potent cardiac stimulant with low efficacy.
Russell
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The National Heart Foundation and Prince Charles Hospital Foundation Cardiovascular Research Centre, Department of Medicine, The Prince Charles Hospital, Chermside, Queensland 4032, Australia. russell@medicine.uq.edu.au
Molenaar
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O'Brien
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D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D014579:Urotensins / Q000494:pharmacology*
D002316:Cardiotonic Agents; D014579:Urotensins; C029677:urotensin II