A selective type V phosphodiesterase inhibitor, E4021, protects the development of right ventricular overload and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension.
We evaluated the effects of oral administration of 10, 30, and 100 mg/kg/day of E4021, a type V phosphodiesterase inhibitor, on development of monocrotaline-induced right ventricular overload and medial thickening of pulmonary arteries. Right ventricular systolic pressure, mass ratio of right ventricle to left ventricle, right ventricular wall thickness, right ventricular myocardial fiber diameter, medial thickness, and smooth muscle area in pulmonary arteries were significantly less in rats that received E4021 30 and 100 mg/kg/day than in the control with monocrotaline on day 28. Myofiber diameter, medial thickness, and smooth muscle area were significantly lower in rats treated with E4021 100 mg/kg/day than in those of E4021 30 mg/kg/day. E4021 100 mg/kg/day protected development of right ventricular overload and medial thickening of pulmonary arteries.
Takahashi
T
T
Second Department of Internal Medicine, Gunma University School of Medicine, Japan.
Kanda
T
T
Inoue
M
M
Suzuki
T
T
Kobayashi
I
I
Kodama
K
K
Nagai
R
R
D000818:Animals; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009929:Organ Size; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C091517:E 4021; D010726:Phosphodiesterase Inhibitors; D010880:Piperidines; D011799:Quinazolines; D016686:Monocrotaline