Open AccessDDCI‐01, a novel long acting phospdiesterase‐5 inhibitor, attenuated monocrotaline‐induced pulmonary hypertension in rats
Author(s) -
Li Ailing,
Zhu Zhongkai,
He Yangke,
Dong Qian,
Tang Dianyong,
Chen Zhongzhu,
Huang Wei
Publication year - 2020
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.1177/2045894020939842
Subject(s) - medicine , tadalafil , pulmonary hypertension , right ventricular hypertrophy , ventricle , cyclic guanosine monophosphate , vascular resistance , lung , hemodynamics , ambrisentan , sildenafil , ventricular pressure , cardiology , anesthesia , nitric oxide , bosentan , endothelin receptor , receptor
Pulmonary arterial hypertension is a progressive, malignant heart disease, characterized by pulmonary arteriole remodeling and increased pulmonary vascular resistance, which eventually leads to right heart failure. This study sought to evaluate the effects of a novel long‐acting phospdiesterase‐5 inhibitor, namely DDCI‐01, as an early intervention for monocrotaline‐induced pulmonary hypertensive rats. To establish this model, 50 mg/kg of monocrotaline was intraperitoneally injected into rats. At Day 7 after monocrotaline injection, two doses of DDCI‐01 (3 or 9 mg/kg/day) or tadalafil (at 3 or 9 mg/kg/day) were intragastrically administered. The rats were anesthetized with pentobarbital for hemodynamic and echocardiographic measurements, at Day 21 after monocrotaline injection. Compared to the monocrotaline group, DDCI‐01 at 3 and 9 mg/kg/day (P) reduced the mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure, right ventricular transverse diameter, pulmonary arterial medial wall thickness (WT%), and right ventricle hypertrophy. However, no significant difference in the indices mentioned as above was found between DDCI‐01 (3 mg/kg/day) and tadalafil (3 mg/kg/day). In addition, DDCI‐01 at 9 mg/kg/day resulted in lower mPAP and WT%, as well as higher cyclic guanosine monophosphate levels in the lung and plasma compared with the same dose of tadalafil (9 mg/kg/day) (all P < 0.05). These findings suggested that DDCI‐01 improved monocrotaline‐induced pulmonary hypertension in rats, and a dose of DDCI‐01 of 9 mg/kg/day might be more effective than the same dose of tadalafil in monocrotaline‐induced pulmonary hypertension in rats.