DDCI-01, a novel long acting phospdiesterase-5 inhibitor, attenuated monocrotaline-induced pulmonary hypertension in rats

Autor: Ailing Li, Zhongkai Zhu, Yangke He, Qian Dong, Dianyong Tang, Zhongzhu Chen, Wei Huang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Pulmonary Circulation, Vol 10 (2020)
Druh dokumentu: article
ISSN: 2045-8940
20458940
DOI: 10.1177/2045894020939842
Popis: 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
Databáze: Directory of Open Access Journals
Externí odkaz: