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心力衰竭中的多巴胺与肾脏

Dopamine and the kidney in heart failure.

作者信息

Casagrande C

机构信息

Simes Cardiovascular Research Centre, Zambon Research, Cormano, Milano.

出版信息

Herz. 1991 Apr;16(2):102-15.

PMID:2066052
Abstract

Dopamine, administered as in intravenous infusion, has shown unique pharmacological properties in the cardiovascular and renal system with respect to the other catecholamines. These properties, which are the basis of its clinical use, have been related to the stimulation not only of beta- and alpha-adrenergic receptors, but of specific dopamine receptors, particularly when dopamine is administered at a low rate of infusion (0.5 to 2 micrograms/kg.min). Peripheral dopamine receptors of the DA1 and DA2 subtype are located in the arterial bed, in prejunctional sympathetic fibres, and probably on specific dopaminergic neurons, and mediate vasodilation either directly or through the control of sympathetic tone. DA1 and DA2 receptors are also located in the kidney and are involved in the control of electrolyte excretion and in renin release; in the adrenal cortex, DA2 receptors exert control on aldosterone release. These findings, and the local synthesis of dopamine in the proximal tubular cells, strongly suggest a physiological role of dopamine in cardiovascular-renal homeostasis in health and disease. Various efforts of expanding and improving the therapeutic use of dopamine have allowed important progress in the understanding of dopaminergic mechanisms in laboratory and clinical pharmacology; the selective DA1 agonist fenoldopam and gludopa, a prodrug delivering dopamine to the kidney, have been particularly useful in this respect. Ibopamine, a prodrug which is able to produce dopamine-like effects on oral administration, has proved its clinical usefulness in the chronic treatment of congestive heart failure, as a monotherapy in mildly affected patient, or in combination therapy in severe patients. In the light of these, and other, results the importance of further effort in pathophysiological and therapeutic research in this field has to be emphasized.

摘要

静脉输注多巴胺时,相对于其他儿茶酚胺类物质,它在心血管系统和肾脏系统中表现出独特的药理特性。这些特性是其临床应用的基础,不仅与β-和α-肾上腺素能受体的刺激有关,还与特定的多巴胺受体的刺激有关,尤其是当以低输注速率(0.5至2微克/千克·分钟)给予多巴胺时。DA1和DA2亚型的外周多巴胺受体位于动脉床、节前交感神经纤维以及可能特定的多巴胺能神经元上,可直接或通过控制交感神经张力来介导血管舒张。DA1和DA2受体也位于肾脏中,参与电解质排泄的控制和肾素释放;在肾上腺皮质中,DA2受体对醛固酮释放起控制作用。这些发现以及近端肾小管细胞中多巴胺的局部合成,有力地表明多巴胺在健康和疾病状态下的心血管-肾脏稳态中具有生理作用。为扩大和改善多巴胺的治疗用途所做的各种努力,在实验室和临床药理学中对多巴胺能机制的理解方面取得了重要进展;选择性DA1激动剂非诺多泮和将多巴胺递送至肾脏的前体药物格鲁多巴在这方面特别有用。异波帕明是一种口服时能够产生类似多巴胺作用的前体药物,已证明其在充血性心力衰竭的慢性治疗中具有临床实用性,可作为轻度患者的单一疗法,或重度患者的联合疗法。鉴于这些及其他结果,必须强调在该领域进一步开展病理生理学和治疗研究的重要性。

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