Evaluation of the preventive effect of DL0805-2 against monocrotaline induced rat pulmonary arterial hypertension
10.16438/j.0513-4870.2020-0981
- VernacularTitle:DL0805-2防治野百合碱诱导的大鼠肺动脉高压的药效评价
- Author:
Di CHEN
;
Tian-yi YUAN
;
Yu-cai CHEN
;
Hui-fang ZHANG
;
Zi-ran NIU
;
Lian-hua FANG
;
Guan-hua DU
- Publication Type:Research Article
- Keywords:
DL0805-2;
pulmonary hypertension;
right ventricular systolic pressure;
pulmonary artery remodeling;
Rho-kinase pathway
- From:
Acta Pharmaceutica Sinica
2021;56(1):208-216
- CountryChina
- Language:Chinese
-
Abstract:
In the treatment of hypertensive crisis, the novel Rho kinase inhibitor DL0805-2 can rapidly lower systematic blood pressure, reduce pulmonary artery pressure, and has a significant protective effect on lung injury. This experiment intends to evaluate the efficacy of DL0805-2 against pulmonary arterial hypertension (PAH) and preliminarily reveals its underlying mechanism. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Sprague Dawley (SD) rats were randomly divided into DL0805-2 low, medium, and high dose groups (1, 3, and 10 mg·kg-1), bosentan positive control group, model group, and blank control group. The drug was administered daily on the 7th day after model establishment by monocrotaline injection. On the 25th day of the experiment, relevant indicators were examined to observe the therapeutic effect of DL0805-2 on pulmonary hypertension. DL0805-2 significantly relieved the abnormal changes in the physiological parameters related to PAH induced by monocrotaline, including reducing right ventricular systolic pressure, alleviating cardiac damage caused by pressure overload, and reducing the levels of endothelin-1 and inflammatory factors in lung tissues. DL0805-2 also attenuated pulmonary arteries remodeling. It was preliminarily discovered that DL0805-2 exerts preventive and therapeutic effect on PAH through Rho-kinase pathway. Our results suggested that DL0805-2 had good therapeutic effects on monocrotaline-induced PAH rat model. It intervened early in the disease process, effectively prevented the development of the disease, and reduced the mortality of the diseased animals. The mechanism is related to Rho-kinase pathway.
