Altschuld R A, Billman G E
Department of Medical Biochemistry, The Ohio State University College of Medicine and Public Health, 333 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210-1218,
Pharmacol Ther. 2000 Oct;88(1):1-14. doi: 10.1016/s0163-7258(00)00075-9.
beta-Adrenoceptor antagonists significantly reduce the incidence of sudden cardiac death in patients with contractile dysfunction. Contractile dysfunction is associated with a decline in beta(1)-adrenoceptors, no change in the number of beta(2)-adrenoceptors, and an increased responsiveness to beta(2)-adrenoceptor stimulation. Selective beta(2)-adrenoceptor blockade prevents ventricular fibrillation in a canine model of sudden cardiac death. Cardiac beta(2)-adrenoceptor stimulation increases L-type Ca(2+) currents, but unlike beta(1)-adrenoceptor stimulation, it fails to elicit phospholamban phosphorylation. Restoration of resting diastolic [Ca(2+)] following beta(2)-adrenoceptor-mediated increases in Ca(2+) influx is more dependent on Na(+)/Ca(2+) exchange, which generates an arrhythmogenic transient inward current that can trigger ventricular fibrillation.
β-肾上腺素能受体拮抗剂可显著降低收缩功能障碍患者心源性猝死的发生率。收缩功能障碍与β1-肾上腺素能受体数量减少、β2-肾上腺素能受体数量无变化以及对β2-肾上腺素能受体刺激的反应性增加有关。选择性β2-肾上腺素能受体阻滞可预防犬心源性猝死模型中的室颤。心脏β2-肾上腺素能受体刺激可增加L型Ca2+电流，但与β1-肾上腺素能受体刺激不同，它不能引起受磷蛋白磷酸化。β2-肾上腺素能受体介导的Ca2+内流增加后，静息舒张期[Ca2+]的恢复更多地依赖于Na+/Ca2+交换，这会产生一种致心律失常的短暂内向电流，可触发室颤。
