DICP OpenIR
Rolipram, a PDE4 Inhibitor, Enhances the Inotropic Effect of Rat Heart by Activating SERCA2a
Huang, Huili1; Xie, Ming1; Gao, Li1; Zhang, Wenhui1; Zhu, Xiaojia1; Wang, Yuwei1; Li, Wei1; Wang, Rongrong2,3; Chen, Kesu4; Boutjdir, Mohamed5,6,7; Chen, Long1,8
Corresponding AuthorChen, Long(longchcn@njucm.edu.cn)
KeywordPDE4 rolipram P-V loop Ca2+ transient SERCA2a
Source PublicationFRONTIERS IN PHARMACOLOGY
2019-03-22
ISSN1663-9812
DOI10.3389/fphar.2019.00221
Volume10Pages:12
Funding Project113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City[2016024] ; National Natural Science Foundation of China[81573304]
Funding Organization113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS SubjectPharmacology & Pharmacy
WOS Research AreaPharmacology & Pharmacy
WOS KeywordCYCLIC-NUCLEOTIDE PHOSPHODIESTERASE ; CA2+ RELEASE ; CAMP ; MICRODOMAINS
AbstractThis study was designed to investigate the hemodynamic effect of rolipram, a phosphodiesterase type 4 (PDE4) inhibitor, in normal rat hearts both in vivo and in vitro and its underlying mechanism. The pressure-volume loop, isolated heart, and Ca2+ transients triggered by field stimulation or caffeine were used to analyze the hemodynamic mechanism of rolipram. The results demonstrated that rolipram (3 mg/kg, ip) significantly increased the in vivo rat heart contractility by enhancing stroke work, cardiac output, stroke volume, end-systolic volume, end-diastolic volume, end-systolic pressure, heart rate, ejection fraction, peak rate of rise of left pressure (+dp/dt(max)), the slopes of end-systolic pressure-volume relationship (slope of ESPVR) named as left ventricular end-systolic elastance, and reduced the slopes of end-diastolic pressure-volume relationship (slope of EDPVR). Meanwhile, the systolic blood pressure, diastolic blood pressure, and pulse pressure were significantly enhanced by rolipram. Also, rolipram deviated normal ventricular-arterial coupling without changing the arterial elastance. Furthermore, rolipram (0.1, 1, 10 mu M) also exerted positive inotropic effect in isolated rat hearts by increasing the left ventricular development pressure, and +dp/dt(max) in non-paced and paced modes. Rolipram (10 mu M) increased the SERCA2a activity, Ca(2+ )content, and Ca(2+ )leak rate without changing diastolic Ca2+ level. Rolipram had significant positive inotropic effect with less effect on peripheral vascular elastance and its underlying mechanism was mediated by increasing SERCA2a activity. PDE4 inhibition by rolipram resulted in a positive inotropic effect and might serve as a target for developing agents for the treatment of heart failure in clinical settings.
Language英语
Funding Organization113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; 113 Talent Project of the Fourth Round High Level Innovation Program in Taizhou China Medical City ; National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS IDWOS:000462159200001
PublisherFRONTIERS MEDIA SA
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/165705
Collection中国科学院大连化学物理研究所
Corresponding AuthorChen, Long
Affiliation1.Nanjing Univ Chinese Med, Natl Stand Lab Pharmacol Chinese Mat Med, Sch Pharm, Nanjing, Jiangsu, Peoples R China
2.Dalian Inst Chem Phys, Dalian, Peoples R China
3.Chinese Acad Sci, Biomed Innovat Inst China Med City, Taizhou, Peoples R China
4.Nanjing Mil Command Reg, Dept Resp, Inpatient Wards Senior Cadres, Nanjing Gen Hosp, Nanjing, Jiangsu, Peoples R China
5.VA New York Harbor Healthcare Syst, New York, NY USA
6.Suny Downstate Med Ctr, New York, NY USA
7.NYU, Sch Med, New York, NY USA
8.Inst Chinese Med Taizhou China Med City, Taizhou, Peoples R China
Recommended Citation
GB/T 7714
Huang, Huili,Xie, Ming,Gao, Li,et al. Rolipram, a PDE4 Inhibitor, Enhances the Inotropic Effect of Rat Heart by Activating SERCA2a[J]. FRONTIERS IN PHARMACOLOGY,2019,10:12.
APA Huang, Huili.,Xie, Ming.,Gao, Li.,Zhang, Wenhui.,Zhu, Xiaojia.,...&Chen, Long.(2019).Rolipram, a PDE4 Inhibitor, Enhances the Inotropic Effect of Rat Heart by Activating SERCA2a.FRONTIERS IN PHARMACOLOGY,10,12.
MLA Huang, Huili,et al."Rolipram, a PDE4 Inhibitor, Enhances the Inotropic Effect of Rat Heart by Activating SERCA2a".FRONTIERS IN PHARMACOLOGY 10(2019):12.
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