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The change of the β-adrenergic receptor-adenylate cyclase coupling in the heart failure patients treated with β-blocker
J Mol O-29-8
Cell
Cardiol
24 (Supplement
I) (1992)
CARDIOMYOCYTE ELECTROPHYSIOLOGICAL OBSERVATION IN EXPERIMENTAL COXACKIE B-3 VIRAL MYOCARDITIS Ying-zhen Yang, Di Guo. Li, Pein Yin, Wei-zhong Wu, Hao-zhen Chen. TaI-sheng zhoU*, Jian zharlg* Shanghai I nsmute cf Cardiovascular Diseases, Zhong-Shan Hospital. Shanghai Medical University; *Shanghai Institute of Physiology, Chinese Academy cf Sciences, Shanghai, P.R.China Electrophyslologic s&on of right ventricular myccerdium were examined by standard intracellular microelectrode technique and real-time microcomputer data processor system in BALBfc mice infsoted with ccxackie E-3 virus from 3 days to 9 months. It was found that electrophysiologic parameters cf action pctential changed very quickly at the early stage (3 days to 3 months) cf the dissase. Those abnormahties became mcst apparent by the 7-14th day, including the decrease cf rest pctential (RP), maximum upstroke rate (Vmax), overshoot (OS) end amplitude of action potential (APA), and prolongation cf action pabential duration (APDSO and APDlM)). Meanwhile, patterns cf abnormal action pctentlal (i.e.RP depolarization, delayed afterrepolarized after-hyperpolariion, depolarization, depressed fast response actionpotential, early after-depolaritetlon, lengthening In action potential duration, etc) occurred frequently through the same periods. At the late stage (3-9 months), especially 5 months after infect!on, the electrophysiological parsmeters were nearly normal, the degree and numbers of myccardial lesion dscreess apparently, while the abnormal patterns of action potential were still found. However, they were improved gradually.
o-30-1 EFFECX OF BBIQCKADE CARDIOMYOPATBY
ON B-~RDI~NSIYINA~
MODELOFDBATBD
Makoto Tominaga, Akira Matsumori. 3rd Internal Medicine, Kyoto University, Kyoto, JAPAN Carteolol, a noosoloctive B-blocker with intriosic sympathomimetic activity, has boon shown to be more effoctivo io a mu&e model of dilated cardiomyopathy induced by ence.phalomyocarditis @MC!) virus myocarditis &an metoprolol. To investigate the me&a&m of the effoot of carteolol, B-receptor assay of myccardiom was performed. Four-week-old male DBA/2 mioo were inoculated with the EMC virus and carteolol 1,lO mgikg, metoprolol30 mg/kg or distilled water was given daily, starting oo day 14. Mice wore killed on day 104 and hearts wore excised. Age matched nooinfe.oted mice wore used as controL B-receptor assay of myocardiom was performed with (135I]iodocyanopindolol (ICYP) and then maximum binding (Bma) and dissociation constant (IQ) wore determined. Below are the rot&s. m B 20.9k4.5, 33.1 f 11.1 Normal control 6” 9.855.5 Infected control 5 29.228.1 Metoprolol30 mgAtg 6 14.3 f 6.0 21.5kl4.2 Carte0101 1 mg/kg 6 19.3 k3.3 + 213 2 5.3 Carte.olol 10 ma/lrp. 6 22.3+3.1',** 23.92 l5.0 *pcO.Olvs Infected control, "pt0.05 vsMetoprolol, +piO.OS vsInfectedcontrol This study suggests that carteolol is more effective in a dose dependent manner for up-regulation of B-recap tor of myocardium io dilated cardiomyopathy than metoprolol.
o-3@2TITE
CHANGE OF TBE 8-ABRENERGIC RECEPTGR-ABRNYLATE TBE BEART FAILURE PATIENTS TREATEB WITH 8-BLOCKER.
CYCLASE COWLING
IN
Katsuomi Takahisa Yasushi To adrenergic
Iwakura, Masatake Fukunami, Masaharu Ohmori, Kazuaki Kumagai, Yamada, Nobuhiko Kondoh, Tetsuo Minamino, Eiichiroh Tsujimura. Abe, Noritake Hoki. Osaka Prefectural Hospital, Osaka, Japan therapy on the f3 investigate the effects of the H-blocker receptor (R). adenylate cyclase (AC) and R-AC coupling, metoprolol (60mg/day) was given daily to 12 patients with DCM (NYHA IIIII) and peripheral lymphocytes were collected before and 1. 2, and 3 administration. xhe number of g-receptors (Bmax) was months after measured using a radioligand I HlCGP12177. and CAMP nroduction was measured withradioimmunoassay in the cells stimulated with 10V4M isoproterenol (ISP-AcAMP) or 10W4M forskolin (FK-&). Bmax and ISP-
CAMP were significantly higher through 1 to 3 months than those before the therapy while no changes in FK-ACAMP were observed. The efficacy of R-AC coupling, which was determined as ISP-A cAMP/Bmax, was significantly greater only at the first month of the therapy. These results indicate that at the early phase B-blocker might improve not onlv B-receutor number but also R-AC coupling leading to an increase This mechanism might play an the- sensitivity to cathecholamine. important
role
in
the
beneficial
effects S.123
of
S-blocker
therapy.
Cell
Cardiol
24 (Supplement
I) (1992)
CARDIOMYOCYTE ELECTROPHYSIOLOGICAL OBSERVATION IN EXPERIMENTAL COXACKIE B-3 VIRAL MYOCARDITIS Ying-zhen Yang, Di Guo. Li, Pein Yin, Wei-zhong Wu, Hao-zhen Chen. TaI-sheng zhoU*, Jian zharlg* Shanghai I nsmute cf Cardiovascular Diseases, Zhong-Shan Hospital. Shanghai Medical University; *Shanghai Institute of Physiology, Chinese Academy cf Sciences, Shanghai, P.R.China Electrophyslologic s&on of right ventricular myccerdium were examined by standard intracellular microelectrode technique and real-time microcomputer data processor system in BALBfc mice infsoted with ccxackie E-3 virus from 3 days to 9 months. It was found that electrophysiologic parameters cf action pctential changed very quickly at the early stage (3 days to 3 months) cf the dissase. Those abnormahties became mcst apparent by the 7-14th day, including the decrease cf rest pctential (RP), maximum upstroke rate (Vmax), overshoot (OS) end amplitude of action potential (APA), and prolongation cf action pabential duration (APDSO and APDlM)). Meanwhile, patterns cf abnormal action pctentlal (i.e.RP depolarization, delayed afterrepolarized after-hyperpolariion, depolarization, depressed fast response actionpotential, early after-depolaritetlon, lengthening In action potential duration, etc) occurred frequently through the same periods. At the late stage (3-9 months), especially 5 months after infect!on, the electrophysiological parsmeters were nearly normal, the degree and numbers of myccardial lesion dscreess apparently, while the abnormal patterns of action potential were still found. However, they were improved gradually.
o-30-1 EFFECX OF BBIQCKADE CARDIOMYOPATBY
ON B-~RDI~NSIYINA~
MODELOFDBATBD
Makoto Tominaga, Akira Matsumori. 3rd Internal Medicine, Kyoto University, Kyoto, JAPAN Carteolol, a noosoloctive B-blocker with intriosic sympathomimetic activity, has boon shown to be more effoctivo io a mu&e model of dilated cardiomyopathy induced by ence.phalomyocarditis @MC!) virus myocarditis &an metoprolol. To investigate the me&a&m of the effoot of carteolol, B-receptor assay of myccardiom was performed. Four-week-old male DBA/2 mioo were inoculated with the EMC virus and carteolol 1,lO mgikg, metoprolol30 mg/kg or distilled water was given daily, starting oo day 14. Mice wore killed on day 104 and hearts wore excised. Age matched nooinfe.oted mice wore used as controL B-receptor assay of myocardiom was performed with (135I]iodocyanopindolol (ICYP) and then maximum binding (Bma) and dissociation constant (IQ) wore determined. Below are the rot&s. m B 20.9k4.5, 33.1 f 11.1 Normal control 6” 9.855.5 Infected control 5 29.228.1 Metoprolol30 mgAtg 6 14.3 f 6.0 21.5kl4.2 Carte0101 1 mg/kg 6 19.3 k3.3 + 213 2 5.3 Carte.olol 10 ma/lrp. 6 22.3+3.1',** 23.92 l5.0 *pcO.Olvs Infected control, "pt0.05 vsMetoprolol, +piO.OS vsInfectedcontrol This study suggests that carteolol is more effective in a dose dependent manner for up-regulation of B-recap tor of myocardium io dilated cardiomyopathy than metoprolol.
o-3@2TITE
CHANGE OF TBE 8-ABRENERGIC RECEPTGR-ABRNYLATE TBE BEART FAILURE PATIENTS TREATEB WITH 8-BLOCKER.
CYCLASE COWLING
IN
Katsuomi Takahisa Yasushi To adrenergic
Iwakura, Masatake Fukunami, Masaharu Ohmori, Kazuaki Kumagai, Yamada, Nobuhiko Kondoh, Tetsuo Minamino, Eiichiroh Tsujimura. Abe, Noritake Hoki. Osaka Prefectural Hospital, Osaka, Japan therapy on the f3 investigate the effects of the H-blocker receptor (R). adenylate cyclase (AC) and R-AC coupling, metoprolol (60mg/day) was given daily to 12 patients with DCM (NYHA IIIII) and peripheral lymphocytes were collected before and 1. 2, and 3 administration. xhe number of g-receptors (Bmax) was months after measured using a radioligand I HlCGP12177. and CAMP nroduction was measured withradioimmunoassay in the cells stimulated with 10V4M isoproterenol (ISP-AcAMP) or 10W4M forskolin (FK-&). Bmax and ISP-
CAMP were significantly higher through 1 to 3 months than those before the therapy while no changes in FK-ACAMP were observed. The efficacy of R-AC coupling, which was determined as ISP-A cAMP/Bmax, was significantly greater only at the first month of the therapy. These results indicate that at the early phase B-blocker might improve not onlv B-receutor number but also R-AC coupling leading to an increase This mechanism might play an the- sensitivity to cathecholamine. important
role
in
the
beneficial
effects S.123
of
S-blocker
therapy.