Jaillon P
Unité de Pharmacologie Clinique, Hôpital Saint-Antoine, Paris.
Ann Cardiol Angeiol (Paris). 1987 Dec;36(10):571-6.
Failure of the myocardial pump and poor adjustment of the cardiac output to the oxygen needs of the body, cause sympathetic reflexes (tachycardia and muscular, cutaneous, splanchnic and renal vasoconstriction) which concur to increase arterial blood pressure and cardiac output. This sympathetic hyperstimulation during the evolution of cardiac insufficiency results in many myocardial consequences: increase of the post-charge and cardiac work, depletion of the stock of neuromediator (nor-epinephrine) in the nerve endings of the myocardial sympathetic fibers and decrease of the number of beta-adrenergic receptors of the myocardial cell membranes. It is well known, now, that the "down-regulation" of beta-receptors involves, at least for a short time, a process of internalization of the receptors when subjected to intense stimulation by agonists receptors. A cell enzyme, the "beta-adrenergic receptor kinase" (BARK) causes a phosphorylation of certain sites of the proteins of the beta-receptor when stimulated by agonists. The receptor is then internalized in the cell and fails to be stimulated. It will become functional again and accessible under the membrane under the effect of another enzyme, a phosphatase. These pharmacological findings have led cardiologists to propose a beta-blocking treatment in severe forms (stage IV) of cardiac insufficiency. Biopsies of the myocardium in patients awaiting a heart transplant, have shown recently that under beta-blockers, the number of beta-functional receptors increased and this was interpreted as a response of myocardial cells to the blocking of remaining receptors (equivalent to an up-regulation phenomenon). This mechanism has been advocated to explain the excellent results of the treatment in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)
心肌泵功能衰竭以及心输出量无法根据身体的氧需求进行良好调节，会引发交感神经反射（心动过速以及肌肉、皮肤、内脏和肾血管收缩），这些反射共同作用以升高动脉血压和心输出量。在心力衰竭进展过程中的这种交感神经过度刺激会导致许多心肌方面的后果：后负荷和心脏做功增加、心肌交感神经纤维神经末梢中的神经介质（去甲肾上腺素）储备耗竭以及心肌细胞膜β - 肾上腺素能受体数量减少。现在众所周知，β受体的“下调”至少在短时间内涉及受体在受到激动剂受体强烈刺激时的内化过程。一种细胞酶，即“β - 肾上腺素能受体激酶”（BARK），在受到激动剂刺激时会使β受体蛋白的某些位点发生磷酸化。然后受体被内化到细胞内，无法再被刺激。在另一种酶——磷酸酶的作用下，它会再次恢复功能并出现在细胞膜下。这些药理学发现促使心脏病专家对重度（IV期）心力衰竭患者提出β受体阻滞剂治疗方案。最近对等待心脏移植患者的心肌活检显示，在使用β受体阻滞剂的情况下，有功能的β受体数量增加，这被解释为心肌细胞对剩余受体被阻断的一种反应（相当于一种上调现象）。有人主张用这种机制来解释该治疗方法在一些患者中取得的良好效果。（摘要截选至250词）
