Effect of a novel phosphodiesterase type 5 inhibitor, CPD1, on vasoconstriction in rats with pulmonary arterial hypertension
10.3969/j.issn.1001-1978.2021.03.007
- Author:
Hui-Dan ZHU
1
;
Jia-Qi KE
1
;
Jia-Lu WANG
1
;
Jia-Jia XU
1
;
Xiao-Qing LIU
1
;
Jian-Qin YANG
1
;
Allan Zi-Jian ZHAO
1
;
Yun-Ping MU
1
;
Fang-Hong LI
1
Author Information
1. School of Biomedical Arid Pharmaceutical Sciences, Guangdong University of Technology
- Publication Type:Journal Article
- Keywords:
aorta;
calcium channel;
contraction;
phosphodiesterase type 5 inhibitors;
pulmonary arterial hypertension;
pulmonary artery
- From:
Chinese Pharmacological Bulletin
2021;37(3):328-337
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effect of CPD1 , a novel phosphodiesterase 5 inhibitor, on contractile ten- sion of pulmonary artery and aorta in rats with pulmonary arterial hypertension ( PAH ) .Methods MCT- induced PAH was generated by a single intraperitoneal injection of MCT(50 mg • kg"1) in rats.Seven days after MCT injection, the rats were treated with CPD1 ( 10 mg • kg-1 • d"1) for 14 days.The tension of vascular rings was examined in MCT-induced PAH rats.Results MCT treated rats exhibited profound PAH when examined 3 weeks after injection.In contrast, gavage administration of CPD1 led to significant decrease in the right ventricle systolic pressure ( RVSP) and right ventricular mass index (RVMI), as well as MCT-induced pulmonary arterial wall thinning and enlarged lumen, indicating that CPD1 inhibited the de- velopment of PAH.Cavage administration of CPD1 also reduced phenylephrine and endothelin-1-induced pulmonary artery contraction and aorta contraction in MCT-treated rats.Conclusions Treatment with CPD1 attenuates vascular reactivity, lessens vascular smooth muscle cell proliferation and remodeling, and inhibits PAH via inhibition of non-voltage dependent Ca2∗ channels in normal and PAH rats.