Francis G S
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.
Clin Cardiol. 1995 Mar;18(3 Suppl I):I13-6. doi: 10.1002/clc.4960181305.
The sympathetic nervous system is under extraordinarily complex modulation, involving numerous presynaptic and postsynpatic control mechanisms. These highly conserved and very redundant control mechanisms allow for the sympathetic nervous system to adapt quickly and precisely to altered environmental stress or conditions. Heart failure (HF) is characterized by excessive sympathetic activity, with both enhanced "spillover" and reduced clearance of norepinephrine (NE). The normal inhibitor control mechanisms appear faulty, with unleashed sympathetic activity likely contributing to the pathophysiology of the clinical syndrome and being associated with excessive mortality. Attempts to attenuate pharmacologically the release or "spillover" of NE from sympathetic neurons in HF has remained an attractive therapeutic strategy, and various alpha 2 adrenergic agonists and dopaminergic agents have been studied in several small clinical trials. Agents designed to activate both presynaptic (DA2) and postsynaptic or vascular (DA1) receptors have demonstrated promise. Ibopamine, a prodrug that is converted metabolically to epinine, a DA1 > DA2 agonist, has potential for selective vasodilation of mesenteric, renal, cerebral, and coronary vascular beds while reducing NE release and aldosterone activity. Preliminary clinical trials with ibopamine are encouraging, but placebo-controlled multicenter studies will be necessary to establish its role in the treatment of HF.
交感神经系统受到极其复杂的调节，涉及众多突触前和突触后控制机制。这些高度保守且冗余的控制机制使交感神经系统能够快速、精确地适应环境应激或条件的改变。心力衰竭（HF）的特征是交感神经活动过度，去甲肾上腺素（NE）的“溢出”增加且清除减少。正常的抑制控制机制似乎存在缺陷，不受抑制的交感神经活动可能导致临床综合征的病理生理学，并与过高的死亡率相关。在心力衰竭中，通过药理学方法减弱交感神经元释放NE或其“溢出”的尝试一直是一种有吸引力的治疗策略，并且在几项小型临床试验中对各种α2肾上腺素能激动剂和多巴胺能药物进行了研究。设计用于激活突触前（DA2）和突触后或血管（DA1）受体的药物已显示出前景。异波帕明是一种前体药物，经代谢转化为依匹宁，一种DA1>DA2激动剂，具有选择性扩张肠系膜、肾、脑和冠状动脉床血管的潜力，同时减少NE释放和醛固酮活性。异波帕明的初步临床试验令人鼓舞，但需要进行安慰剂对照的多中心研究来确定其在心力衰竭治疗中的作用。
