Down regulation of myocardial β1-adrenoceptor signal transduction system in pacing-induced failure in dogs with aortic stenosis-induced left ventricular hypertrophy
Down regulation of myocardial β1-adrenoceptor signal transduction system in pacing-induced failure in dogs with aortic stenosis-induced left ventricular hypertrophy
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心肌β1-肾上腺素受体信号转导系统的下调在主动脉瓣狭窄引起的左心室肥厚犬起搏引起的失败中
DOI：
10.1023/a:1007085027234
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发表时间：
2000
影响因子：
4.3
通讯作者：
P. Scholz
中科院分区：
文献类型：
--
作者：
J. Tse;Mark W. Huang;R. Leone;H. Weiss;Y. He;P. Scholz
我们最近证明，快速心室起搏导致患有主动脉狭窄诱导的左心室肥大（肥大）的犬心力衰竭（衰竭），异丙肾上腺素未导致衰竭肥大心脏的功能、O2消耗和细胞内环AMP水平显著增加。我们检验了以下假设：在从代偿性肥大到衰竭的转变过程中，β1-肾上腺素能受体信号转导通路的改变与对β-肾上腺素能刺激的功能和代谢反应降低相关。在6个月的时间内，在10只狗中使用主动脉瓣折叠术建立压力超负荷诱导的左心室肥厚。5只犬在主动脉瓣折叠术后5个月，以240 bpm快速心室起搏4周，诱发充血性心力衰竭。与对照组（344 ± 51; 1，551 ± 203）和肥大组（298 ± 33; 1，721 ± 162）犬相比，衰竭组犬（176 ± 19; 755 ± 136）的心肌β1-肾上腺素受体密度（fmol/mg膜蛋白; fmol/g湿组织）显著降低。受体亲和力在所有组之间没有显著差异。衰竭肥厚心脏的β1-肾上腺素能受体百分率（62 ± 3%）较肥厚心脏（77 ± 5%）有轻微但显著的下降。衰竭犬（45 ± 4）的基础心肌腺苷酸环化酶活性（mmol/mg蛋白/min）显著低于对照犬（116 ± 14）和肥厚犬（86 ± 6）。失败犬（158 ± 17）中毛喉素（0.1 mM）刺激的腺苷酸环化酶活性也显著低于对照犬（296 ± 35），略低于肥大犬（215 ± 10）。各组间低Km环腺苷酸磷酸二酯酶活性无显著差异。结论：快速心室起搏引起的肥厚衰竭心脏β1-肾上腺素能受体下调和腺苷酸环化酶活性降低是导致心肌功能和β-肾上腺素能反应降低的原因之一。
We recently demonstrated that rapid ventricular pacing caused cardiac failure (Failure) in dogs with aortic stenosis-induced left ventricular hypertrophy (Hypertrophy) and isoproterenol caused no significant increases in function, O2 consumption and intracellular cyclic AMP level in the failing hypertrophied hearts. We tested the hypothesis that alterations in the β1-adrenoceptor-signal transduction pathway would correlate with the reduced functional and metabolic responses to β-adrenergic stimulation during the transition from the compensated hypertrophy to failure. Pressure overload-induced left ventricular hypertrophy was created using aortic valve plication in 10 dogs over a 6-month period. Five months after aortic valve plication, congestive heart failure was induced in 5 dogs by rapid ventricular pacing at 240 bpm for 4 weeks. The density of myocardial β1-adrenoceptors (fmoles/mg membrane protein; fmoles/g wet tissue) was significantly reduced in the Failure dogs (176 ± 19; 755 ± 136) when compared to those of the Control (344 ± 51; 1,551 ± 203) and the Hypertrophy (298 ± 33; 1,721 ± 162) dogs. The receptor affinities were not significantly different among all groups. There was a small but significant decrease in the percentage of β1-adrenoceptors of the failing hypertrophied hearts (62 ± 3%) when compared to that of the hypertrophied hearts (77 ± 5%). The basal myocardial adenylyl cyclase activity (rmoles/mg protein/min) was significantly lower in the Failure dogs (45 ± 4) than in the Control (116 ± 14) and Hypertrophy (86 ± 6) dogs. The forskolin (0.1 mM)-stimulated adenylyl cyclase activity was also significantly lower in the Failure dogs (158 ± 17) than in the Control dogs (296 ± 35) and slightly lower than in the Hypertrophy dogs (215 ± 10). There were no significant differences in low Km cyclic AMP-phosphodiesterase activities among all groups. We conclude that down regulation of β1-adrenoceptors and reduced adenylyl cyclase activities contribute to the decreases in myocardial functions and β-adrenergic responses in the failing hypertrophied hearts induced by rapid ventricular pacing.
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影响因子：
20.1
作者：
MARZO, KP;FREY, MJ;MOLINOFF, PB
通讯作者：
MOLINOFF, PB
影响因子：
37.8
作者：
FOWLER, MB;LASER, JA;BRISTOW, MR
通讯作者：
BRISTOW, MR
非衰竭和衰竭人类心室心肌中的β-肾上腺素能通路。
影响因子：
37.8
作者：
Bristow,MR;Hershberger,RE;Port,JD;Gilbert,EM;Sandoval,A;Rasmussen,R;Cates,AE;Feldman,AM
通讯作者：
Feldman,AM
影响因子：
20.1
作者：
BRISTOW, MR;GINSBURG, R;STINSON, EB
通讯作者：
STINSON, EB
DOI：
--
发表时间：
1988
期刊：
Advances in second messenger and phosphoprotein research
影响因子：
--
作者：
Beavo Ja
通讯作者：
Beavo Ja