title: Calcium handling and role of endothelin-1 in monocrotaline right ventricular hypertrophy of the rat.
abstract: We investigated the role of endothelin-1 (ET-1) in right ventricular function and intracellular Ca(2+)(Ca(2+)(i)) handling of isolated perfused rat hearts with right ventricular hypertrophy induced by monocrotaline (50 mg/kg). Nine weeks after monocrotaline (n=9) or saline (control n=9) treatment, hearts were perfused isovolumically at 37 degrees C and right ventricular function (fluid-filled balloon), right ventricular intracellular Ca(2+) transients (aequorin bioluminescence method) and the effects of ET-1 were determined. Monocrotaline-treated rats developed considerable right ventricular hypertrophy (right ventricular weight:body weight ratio: 1.07+/-0.13 v. 0.60+/-0.03 in controls P<0.05) and these hearts generated higher right ventricular systolic and diastolic pressure, but similar systolic and diastolic wall stress, indicating a compensated functional state. Hypertrophied hearts demonstrated a prolonged duration of isovolumic contraction (time to 90% decline from peak: 105+/-1 v 89+/-4 ms at 3 m M extracellular Ca(2+) P<0.05), but neither the time to peak pressure (71+/-3 ms) nor time to peak light (25+/-3 ms) were different from controls. The increased duration of contraction correlated with a similar prolongation of the Ca(2+)transient (time to 90% decline from peak: 72+/-4 v 50+/-3 ms P<0.05), indicating a reduced rate of Ca(2+)sequestration in hypertrophic right ventricles. Peak systolic intracellular Ca(2+)was similar in control and hypertrophied hearts (1.04+/-0.02 and 0.99+/-0.02 microM, P>0.05, n=6). ET-1 (1-300 p M) affected neither the time course of right ventricular contraction nor that of the Ca(2+)transient or peak systolic Ca(2+)concentrations. These data are the first measurements of right ventricular Ca(2+)transients in beating normal and hypertrophic hearts. We conclude that ET-1 plays no role in compensated hypertrophy because it affected neither right ventricular function nor intracellular Ca(2+)handling in this model.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Universitätsplatz 2, Graz, A-8010, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Wölkart
authors.forename: H
authors.initials: H
authors.lastname: Strömer
authors.forename: F
authors.initials: F
authors.lastname: Brunner
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D003971:Diastole; D019332:Endothelin-1 / Q000494:pharmacology / Q000502:physiology*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D016686:Monocrotaline / Q000633:toxicity*; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole; D016278:Ventricular Function, Right / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D016686:Monocrotaline; D002118:Calcium