Lokhandwala M F, Hegde S S
Department of Pharmacology, University of Houston, TX 77204-5515.
Am J Med. 1991 May 29;90(5B):2S-9S. doi: 10.1016/0002-9343(91)90265-y.
This review discusses the localization of adrenergic- and dopaminergic-adrenoceptors within the cardiovascular system and describes the cardiovascular and renal changes produced following the activation of these receptors by appropriate agonists. Whereas the role of alpha- and beta-adrenergic agents in the treatment of heart failure is well recognized, recent studies with dopamine (DA)-receptor agonists indicate that they offer a novel approach in the therapy of congestive heart failure. DA-adrenoceptor agonists reduce afterload by causing vasodilation and promote sodium excretion via direct activation of DA1-adrenoceptors located on renal tubules. Fenoldopam is a selective DA1-adrenoceptor agonist found to be effective in heart failure. It reduces afterload by causing peripheral vasodilation and produces natriuresis and diuresis. Dopexamine is a DA1- and beta 2-adrenoceptor agonist, and its efficacy in heart failure is due to its ability to provide mild inotropic support and cause a reduction in afterload. Ibopamine is a prodrug that is converted into its active metabolite, epinine. This compound activates primarily DA1- and DA2-adrenoceptors. It is effective in heart failure, and the mechanism progresses via DA1- and DA2-adrenoceptor-mediated reduction in afterload. Agonists of DA2-adrenoceptors reduce afterload by decreasing the release of norepinephrine and by reducing the levels of renin-angiotensin-aldosterone system. Since both of these systems are active in heart failure, ibopamine offers a rational approach for therapy. The present review addresses the concept of pharmacologic intervention in adrenergic and dopaminergic influence in the cardiovascular and renal systems to produce changes that are desirable for the pharmacotherapy of congestive heart failure.
本综述讨论了肾上腺素能和多巴胺能肾上腺素受体在心血管系统中的定位，并描述了这些受体被适当激动剂激活后所产生的心血管和肾脏变化。虽然α和β肾上腺素能药物在治疗心力衰竭中的作用已得到充分认可，但最近关于多巴胺（DA）受体激动剂的研究表明，它们为充血性心力衰竭的治疗提供了一种新方法。DA肾上腺素受体激动剂通过引起血管舒张来降低后负荷，并通过直接激活位于肾小管上的DA1肾上腺素受体促进钠排泄。非诺多泮是一种选择性DA1肾上腺素受体激动剂，已发现其对心力衰竭有效。它通过引起外周血管舒张来降低后负荷，并产生利钠和利尿作用。多培沙明是一种DA1和β2肾上腺素受体激动剂，其在心力衰竭中的疗效归因于其提供轻度正性肌力支持和降低后负荷的能力。异波帕明是一种前药，可转化为其活性代谢物依匹宁。该化合物主要激活DA1和DA2肾上腺素受体。它对心力衰竭有效，其作用机制是通过DA1和DA2肾上腺素受体介导的后负荷降低。DA2肾上腺素受体激动剂通过减少去甲肾上腺素的释放和降低肾素-血管紧张素-醛固酮系统的水平来降低后负荷。由于这两个系统在心力衰竭中均有活性，异波帕明为治疗提供了一种合理的方法。本综述探讨了对心血管和肾脏系统中肾上腺素能和多巴胺能影响进行药物干预的概念，以产生对充血性心力衰竭药物治疗有利的变化。
