The positive inotropic effect of phosphodiesterase type 8 inhibitor of PF-04957325 in rats and its underlying mechanism
10.3969/j.issn.1001-1978.2021.09.014
- Author:
Yu-Jie XIAO
1
;
Qian-Wen GAO
1
;
Yu-Wei WANG
1
;
Xiao-Jia ZHU
1
;
Long CHEN
1
;
Ke-Su CHEN
2
;
Fu-Ming LIU
3
;
Rong-Rong WANG
4
;
Long CHEN
4
Author Information
1. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine
2. Wound Care Centre, Dept of Outpatient, Jinling Hospital, The Affiliated Hospital of Medical School of Nanjing University
3. First Affiliated Hospital, Nanjing University of Chinese Medicine
4. Institute of Chinese Medicine of Taizhou China Medical City
- Publication Type:Journal Article
- Keywords:
Ca;
phosphodiesterase type 8;
Phospholamban;
RyR2;
SERCA2a;
ventricular pressure-volume loop
- From:
Chinese Pharmacological Bulletin
2021;37(9):1264-1270
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the inotropic effect of PF-04957325, a phosphodiesterase type 8 inhibitor, in normal rats and its underlying molecular mechanism. Methods The techniques of in vivo rat left ventricular pressure-volume loop (P-V loop) and isolated perfusion rat heart were used to analyze the hemodynamics and positive inotropic effect of rat hearts. The Ca transient induced by field stimulation was used to analyze the hemodynamics of sarcoplasmic reticulum (SR) Ca + uptaking. Western blot was used to analyze the phosphorylation levels of SR phospolamban (PLB) and ryanodine receptor type 2 (RyR2). Results The P-V loop experiment indicated that PF-04957325 (0.5 mg · kg
