β-肾上腺素能受体亚型在大鼠心肌儿茶酚胺诱导自动节律中的功能拮抗作用。
Functional antagonism of β-adrenoceptor subtypes in the catecholamine-induced automatism in rat myocardium.
机构信息
Center for Biomedical Engineering, and Department of Biomedical Engineering, School of Electrical and Computer Engineering, University of Campinas, Campinas, SP, Brazil.
出版信息
Br J Pharmacol. 2011 Mar;162(6):1314-25. doi: 10.1111/j.1476-5381.2010.01121.x.
BACKGROUND AND PURPOSE
Myocardial automatism and arrhythmias may ensue during strong sympathetic stimulation. We sought to investigate the relevant types of adrenoceptor, as well as the role of phosphodiesterase (PDE) activity, in the production of catecholaminergic automatism in atrial and ventricular rat myocardium.
EXPERIMENTAL APPROACH
The effects of adrenoceptor agonists on the rate of spontaneous contractions (automatic response) and the amplitude of electrically evoked contractions (inotropic response) were determined in left atria and ventricular myocytes isolated from Wistar rats.
KEY RESULTS
Catecholaminergic automatism was Ca(2+) -dependent, as it required a functional sarcoplasmic reticulum to be exhibited. Although both α- and β-adrenoceptor activation caused inotropic stimulation, only β(1) -adrenoceptors seemed to mediate the induction of spontaneous activity. Catecholaminergic automatism was enhanced and suppressed by β(2) -adrenoceptor blockade and stimulation respectively. Inhibition of either PDE3 or PDE4 (by milrinone and rolipram, respectively) potentiated the automatic response of myocytes to catecholamines. However, only rolipram abolished the attenuation of automatism produced by β(2) -adrenoceptor stimulation.
CONCLUSIONS AND IMPLICATIONS
α- and β(2) -adrenoceptors do not seem to be involved in the mediation of catecholaminergic stimulation of spontaneous activity in atrial and ventricular myocardium. However, a functional antagonism of β(1) - and β(2) -adrenoceptor activation was identified, the former mediating catecholaminergic myocardial automatism and the latter attenuating this effect. Results suggest that hydrolysis of cAMP by PDE4 is involved in the protective effect mediated by β(2) -adrenoceptor stimulation.
背景与目的
强烈的交感神经刺激可能导致心肌自动节律和心律失常。我们旨在研究相关的肾上腺素能受体类型，以及磷酸二酯酶（PDE）活性在产生儿茶酚胺能自发性中的作用在心房和心室大鼠心肌中。
实验方法
在从 Wistar 大鼠分离的左心房和心室心肌细胞中，确定了肾上腺素能受体激动剂对自发性收缩（自动反应）率和电诱发收缩幅度（变力反应）的影响。
主要结果
儿茶酚胺能自动节律是 Ca(2+) 依赖性的，因为它需要功能性肌浆网才能表现出来。虽然 α-和 β-肾上腺素能受体激活都引起变力刺激，但似乎只有 β(1) -肾上腺素能受体介导自发性活动的诱导。儿茶酚胺能自动节律被 β(2) -肾上腺素能受体阻断和刺激分别增强和抑制。PDE3 或 PDE4 的抑制（分别通过米力农和罗利普兰）增强了心肌细胞对儿茶酚胺的自动反应。然而，只有罗利普兰消除了 β(2) -肾上腺素能受体刺激产生的自动节律衰减。
结论和意义
α-和 β(2) -肾上腺素能受体似乎不参与介导心房和心室心肌中儿茶酚胺刺激的自发性活动。然而，鉴定出了功能性拮抗 β(1) -和 β(2) -肾上腺素能受体激活，前者介导儿茶酚胺能心肌自动节律，后者减弱这种效应。结果表明，PDE4 水解 cAMP 参与了 β(2) -肾上腺素能受体刺激介导的保护作用。
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