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	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
刊名	Frontiers in pharmacology
	2019-03-22
卷号	10页码:12
关键词	Pde4 Rolipram P-v loop Ca2+ transient Serca2a
ISSN号	1663-9812
DOI	10.3389/fphar.2019.00221
通讯作者	Chen, long(longchcn@njucm.edu.cn)
英文摘要	This 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.
WOS关键词	CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE ; CA2+ RELEASE ; CAMP ; MICRODOMAINS
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Pharmacology & Pharmacy
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000462159200001
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2372627
专题	大连化学物理研究所
通讯作者	Chen, Long
作者单位	1.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
推荐引用方式 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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