DA-8159, a new PDE5 inhibitor, attenuates the development of compensatory right ventricular hypertrophy in a rat model of pulmonary hypertension.
This study evaluated the effect of DA-8159, a new phosphodiesterase 5 inhibitor, on the compensatory development of right ventricular hypertrophy in monocrotaline (MCT)-induced pulmonary hypertension (PH). Rats treated with subcutaneous MCT were divided into three groups, which received DA-8159 1 mg/kg, DA-8159 5 mg/kg or saline-vehicle orally, twice daily for 21 days. The vehicle group demonstrated increased right ventricular weight, pulmonary artery medial wall thickening, myocardial fibrosis, increased plasma cyclic guanosine monophosphate (cGMP) concentration and reduced body weight gains. DA-8159, however, markedly attenuated the compensatory development of right ventricular hypertrophy and pulmonary artery medial wall thickening, amplified the increase in plasma cGMP levels and increased lung cGMP concentrations. In addition, DA-8159 prevented myocardial fibrosis induced by MCT. These results demonstrate that DA-8159 attenuates the compensatory development of right ventricular hypertrophy in a rate model of PH. DA-8159 might, therefore, be a useful treatment option for PH, but its efficacy in humans needs evaluating.
Kang
K K
KK
Research Institutes, Dong-A Pharmaceutical Co. Ltd, Sanggal, Kiheung, Yongin, Kyunggi, South Korea. kangkk@empal.com
Ahn
G J
GJ
Sohn
Y S
YS
Ahn
B O
BO
Kim
W B
WB
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D017380:Hypertrophy, Right Ventricular / Q000473:pathology / Q000517:prevention & control*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000009:adverse effects; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects; D011651:Pulmonary Artery / Q000033:anatomy & histology / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D016686:Monocrotaline; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D011743:Pyrimidines; D013449:Sulfonamides; C517384:Pde5a protein, rat; C419664:udenafil; D000096926:Benzenesulfonamides