ENDOTHELIN-CONVERTING ENZYME-INHIBITOR PROTECTS DEVELOPMENT OF RIGHT-VENTRICULAR OVERLOAD AND MEDIAL THICKENING OF PULMONARY-ARTERIES IN RATS WITH MONOCROTALINE-INDUCED PULMONARY-HYPERTENSION

We evaluated the effects of FR901533, endothelin converting enzyme inh ibitor, on development of right ventricular overload and medial thicke ning of pulmonary arteries in rats with monocrotaline-induced pulmonar y hypertension. Pulmonary hypertension was induced by a single injecti on of monocrotaline (80 mg/kg). Twenty-four hours later (day 1), conti nuous subcutaneous injection of FR901533.(100 mg/kg/day) was started. Right ventricular systolic pressure, mass ratio of right ventricle to left ventricle, right ventricular wall thickness, right ventricular my ocardial fiber diameter, percent medial thickness, and percent smooth muscle area in pulmonary arteries were significantly less in rats that received FR901533 than in the control with monocrotaline on day 28. B oth immunoreactivities of endothelin-l in pulmonary arteries and plasm a endothelin-l levels were observed significantly less in rats treated with FR901533 than in the control with monocrotaline. There were sign ificant increased immunoreactivities of endothelin-B receptor in pulmo nary arteries in rats that received FR901533 as compared with those in the control with monocrotaline. FR901533 (100 mg/kg/day), protected t he development of right ventricular overload and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension. (C) 1998 Elsevier Science Inc.