Luchsinger A, Velasco M, Urbina A, Morillo J, Romero E, Alvarez R, Pieretti O H
Clinical Pharmacology Unit, Vargas Hospital, Caracas-Venezuela.
J Clin Pharmacol. 1992 Jan;32(1):55-60. doi: 10.1002/j.1552-4604.1992.tb03788.x.
The role of dopaminergic receptors on renal function has been extensively studied. Recently dopaminergic receptor has been classified in two subtypes D1 and D2, which seem to have different modulatory function. However, the role of dopaminergic receptors on cardiovascular function and more specifically the potential role of dopaminergic agonists as antihypertensive agents has not yet been clarified. Nine outpatients with mild and moderate hypertension were studied in the Cardiology Service of Vargas Hospital with a D1 agonist, piribedil, at 50-100 mg/day, orally, for 8 weeks, and with a D2 agonist, bromocriptine, at 2.5 - 5 mg/day, orally, for an another 8 weeks by using a placebo comparative crossover design. Piribedil reduced blood pressure with a modest increase in heart rate, plasma renin activity, and of plasma aldosterone, and an important increment of renal function. Bromocriptine reduced blood pressure with a decrease in heart rate and plasma aldosterone without altering renal function. There was no orthostatic hypotension with either agent. The authors conclude that activation of dopaminergic D1 receptor induces a vasodilatory and antihypertensive effect with a reflex increase in sympathetic tone, whereas activation of dopaminergic D2 receptor induces a decrease in sympathetic tone, probably due to a decrease in norepinephrine release at adrenergic endings. The potential effect of these compounds as antihypertensive agents is of great interest because blood pressure reduction can be induced by a new mechanism, i.e. activation of dopaminergic receptors which results in a decrease of the renin angiotensin system or a vasodilatory action.(ABSTRACT TRUNCATED AT 250 WORDS)
多巴胺能受体对肾功能的作用已得到广泛研究。最近,多巴胺能受体被分为D1和D2两种亚型,它们似乎具有不同的调节功能。然而,多巴胺能受体对心血管功能的作用,更具体地说,多巴胺能激动剂作为抗高血压药物的潜在作用尚未阐明。在瓦尔加斯医院心脏病科,采用安慰剂对照交叉设计,对9名轻度和中度高血压门诊患者进行了研究。患者口服D1激动剂匹莫齐特,剂量为50 - 100毫克/天,持续8周;然后口服D2激动剂溴隐亭,剂量为2.5 - 5毫克/天,再持续8周。匹莫齐特降低了血压,同时心率、血浆肾素活性和血浆醛固酮略有增加,肾功能显著增强。溴隐亭降低了血压,心率和血浆醛固酮下降,而肾功能未改变。两种药物均未引起体位性低血压。作者得出结论,多巴胺能D1受体的激活诱导血管舒张和降压作用,并伴有交感神经张力反射性增加,而多巴胺能D2受体的激活导致交感神经张力降低,这可能是由于肾上腺素能末梢去甲肾上腺素释放减少所致。这些化合物作为抗高血压药物的潜在作用备受关注,因为血压降低可通过一种新机制诱导,即激活多巴胺能受体,从而导致肾素 - 血管紧张素系统降低或产生血管舒张作用。(摘要截选至250字)