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 inhibitor, on development of right ventricular overload and medial thickening of pulmonary arteries in rats with monocrotaline-induced pulmonary hypertension. Pulmonary hypertension was induced by a single injection of monocrotaline (80 mg/kg). Twenty-four hours later (day 1), continuous 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 myocardial 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. Both immunoreactivities of endothelin-1 in pulmonary arteries and plasma endothelin-1 levels were observed significantly less in rats treated with FR901533 than in the control with monocrotaline. There were significant increased immunoreactivities of endothelin-B receptor in pulmonary arteries in rats that received FR901533 as compared with those in the control with monocrotaline. FR901533 (100 mg/kg/day), protected the development of right ventricular overload and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension.
Takahashi
T
T
Department of Infectious Diseases, Institute of Medical Science, University of Tokyo, Japan. takahata@ims.u-tokyo.ac.jp
Kanda
T
T
Inoue
M
M
Sumino
H
H
Kobayashi
I
I
Iwamoto
A
A
Nagai
R
R
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects; D000072396:Endothelin-Converting Enzymes; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D006984:Hypertrophy; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008666:Metalloendopeptidases; D016686:Monocrotaline; D009929:Organ Size / Q000187:drug effects; D011042:Poisons; D011651:Pulmonary Artery / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013754:Tetracyclines / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D011042:Poisons; D013754:Tetracyclines; C088494:WS 79089B; D016686:Monocrotaline; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes