Calcium Handling and Role of Endothelin-1 in Monocrotaline Right Ventricular Hypertrophy of the Rat

We investigated the role of endothelin-1 (ET-1) in right ventricular function and intracellular Ca2+(Ca2+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 (controln =9) treatment, hearts were perfused isovolumically at 37°C and right ventricular function (fluid-filled balloon), right ventricular intracellular Ca2+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 extracellular Ca2+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 Ca2+transient (time to 90% decline from peak: 72±4 v 50±3 ms P<0.05), indicating a reduced rate of Ca2+sequestration in hypertrophic right ventricles. Peak systolic intracellular Ca2+was similar in control and hypertrophied hearts (1.04±0.02 and 0.99±0.02 μ, P>0.05, n=6). ET-1 (1–300 p ) affected neither the time course of right ventricular contraction nor that of the Ca2+transient or peak systolic Ca2+concentrations. These data are the first measurements of right ventricular Ca2+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 Ca2+handling in this model.