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


ABSTRACT: 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?

SUBMITTER: Li A 

PROVIDER: S-EPMC7672744 | biostudies-literature | 2020 Oct-Dec

REPOSITORIES: biostudies-literature

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

Li Ailing A   Zhu Zhongkai Z   He Yangke Y   Dong Qian Q   Tang Dianyong D   Chen Zhongzhu Z   Huang Wei W  

Pulmonary circulation 20201001 4


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  ...[more]

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