Forskolin逆转C型钠尿肽对家兔心房机械活动的负性肌力作用  

Forskolin reverses the negative inotropic effects of the C-type natriuretic peptide on rabbit atrial dynamics

作　　者：关成明[1] 贾雅楠[1] 丁大植[1] 崔勋[2] GUAN Chengming JIA Yanan DING Dazhi CUI Xun(Department of Cardiology, Affiliated Hospital of Yanbian University Department of Physiology and Pathophysiology, Yanbian University College of Medicine ： Yanji 133000, Jilin , China)

机构地区：[1]延边大学附属医院心血管内科 [2]延边大学医学院生理学与病理生理学教研部,吉林延吉133000

出　　处：《延边大学医学学报》2016年第4期240-244,共5页Journal of Medical Science Yanbian University

基　　金：吉林省教育厅项目(编号:吉教科合字2015第44号)

摘　　要：[目的]观察腺苷酸环化酶(AC)激活剂Forskolin对C-型钠尿肽(CNP)调节家兔心房机械活动的影响,并探讨其机制.[方法]建立离体搏动家兔心房灌流模型,观察AC激活剂Forskolin、磷酸二酯酶第2(PDE2)及第3亚类型(PDE3)抑制剂EHNA和Milrinone对CNP调节心房机械活动的影响,采用放射免疫法测定环核苷酸含量.[结果]与对照循环比较,CNP(0.03μmol/L)可明显增加心房肌细胞cGMP含量(P<0.001),并显著抑制心房搏出量和搏动压(P<0.01),但cAMP含量则未见明显变化.与对照循环比较,Forskolin(0.1μmol/L)明显增加心房肌细胞cAMP含量(P<0.01),亦显著增高心房搏出量和搏动压(P<0.01).Forskolin+CNP可进一步增加心房肌细胞cAMP含量和心房搏出量及搏动压(P<0.01).与Milrinone+Forskolin比较,Milrinone(10.0μmol/L)+Forskolin+CNP明显降低心房搏出量和搏动压(P<0.05,P<0.01),但心房肌细胞cAMP含量则未见明显变化(P>0.05).而EHNA(100.0μmol/L)未见改变在Forskolin存在下CNP进一步增加心房肌cAMP含量和心房搏出量及搏动压的效应,亦未见影响Milrinone对Forskolin+CNP调节心房肌cAMP含量和心房搏出量及搏动压的效应.[结论]CNP抑制家兔心房机械活动,作用机制认为可能是通过CNP-GC-cGMP信号转导途径来实现的;而Forskolin则可逆转CNP抑制心房机械活动的效应,作用机制可能与CNP-cGMP-PDE3信号通路有关系.OBJECTIVE To observe the effects of adenosine cyclase（AC）activator forsklin on the rabbit atrial dynamics induced by C-type natriuretic peptide（CNP）and explore its mechanism.METHODS The rabbit atrial perfusion models were established.The effects of AC activator forskolin,phosphodiesterase type2（PDE2）and type 3（PDE3）inhibitor EHNA and milrinone on the atrial dynamics induced by CNP were observed.Radioimmunoassay was used to determine the content of cyclic nucleotides.RESULTS As compared with control cycle,CNP（0.03μmol/L）significantly increased atrial cGMP content（P〈0.001）,and obviously decreased atrial stroke volume and pulse pressure（P〈0.01）,but no significant change of the atrial cAMP content was observed.As compared with control cycle,forskolin（0.1μmol/L）significantly increased atrial cAMP content,stroke volume and pulse pressure（P〈0.01）.Forskolin ＋ CNP could further increased atrial cAMP content,atrial stroke volume and pulse pressure（ P〈0.01）.As compared with milrinone ＋ forskolin,milrinone（10.0μmol/L）＋ forskolin ＋ CNP significantly decreased the atrial stroke volume and pulse pressure（P〈0.05,P〈0.01）,but no significant change of the atrial cAMP content was observed（P〉0.05）.While EHNA（100.0μmol/L）failed to alter the effect of CNP on the increase of cAMP content and atrial stroke volume and pulse pressure in the presence of forskolin,and EHNA had also no influence on the effects of milrinone.CONCLUSIONCNP inhibited atrial dynamics via CNP-GC-cGMP signaling pathway,and the forskolin could reverse the inhibitory effects of CNP on atrial dynamics by activation of CNP-cGMP-PDE3 signaling pathway in rabbit.

关 键 词：C型钠尿肽 心房机械活动 环化酶 磷酸二酯酶 环核苷酸 兔 

分 类 号：R331[医药卫生—人体生理学]