Calcium handling and role of endothelin-1 in monocrotaline right ventricular hypertrophy of the rat

We investigated the role of endothelin-l (ET-1) in right ventricular functi on and intracellular Ca2+ (Ca-i(2+)) handling of isolated perfused rat hear ts 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 degreesC and right: ventricular function (fluid-filled balloon), right ventricular intracellular Ca2+ tran sients (aequorin bioluminescence method) and the effects of ET-1 were deter mined. 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 ventri cular systolic and diastolic pressure, but similar systolic and diastolic w all stress, indicating a compensated functional state. Hypertrophied hearts demonstrated a prolonged duration of isovolumic contraction (time to 90% d ecline from peak: 105+/-1 v 89+/-4 ms at 3 mM extracellular Ca2+; P<0.05), but neither the time to peak pressure (71+/-3 ms) nor time to peak light (2 5+/-3 ms) were different from controls. The increased duration of contracti on 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 intr acellular Ca2+ was similar in control and hypertrophied hearts (1.04+/-0.02 and 0.99+/-0.02 <mu>M, P>0.05, n = 6). ET-1 (1-300 pM) affected neither th e time course of right: ventricular contraction nor that: of the Ca2+ trans ient or peak systolic Ca2+ concentrations. These data are the first measure ments of right: ventricular Ca2+ transients in beating normal and hypertrop hic 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. (C) 2000 Academic Press.