Lang C C, Choy A M, Rahman A R, Struthers A D
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, U.K.
Eur Heart J. 1993 Sep;14(9):1245-52. doi: 10.1093/eurheartj/14.9.1245.
Activation of the sympathetic nervous system may contribute to the renal vasoconstriction and sodium retention seen in congestive heart failure. Previous studies in congestive heart failure patients employing large doses of prazosin that lowered systemic blood pressure have been generally disappointing. The renal haemodynamic and segmental tubular effects of low non-depressor doses of prazosin (0.25 mg and 0.50 mg) were examined in eight female patients with mild to moderate congestive heart failure. Segmental tubular function was assessed by the lithium clearance method. Compared to placebo, prazosin caused a significant increase in urinary sodium excretion (from 56 +/- 7 to 92 +/- 7 mumol.min-1, P < 0.01), paralleled by significant increases in fractional excretion of sodium and lithium. Glomerular filtration rate and effective renal plasma flow were not altered by prazosin. Prazosin pre-treatment did not alter any of the renal responses to frusemide treatment (mean dose 85 +/- 14 mg). This study demonstrates that low non-depressor doses of prazosin have a clear natriuretic effect in congestive heart failure patients, which is predominantly established by interference with tubular reabsorption.
交感神经系统的激活可能导致充血性心力衰竭时出现的肾血管收缩和钠潴留。以往对充血性心力衰竭患者使用大剂量哌唑嗪降低全身血压的研究总体上令人失望。在8例轻至中度充血性心力衰竭女性患者中,研究了低剂量非降压剂量哌唑嗪(0.25毫克和0.50毫克)对肾血流动力学和节段性肾小管的影响。采用锂清除率法评估节段性肾小管功能。与安慰剂相比,哌唑嗪使尿钠排泄显著增加(从56±7增加至92±7微摩尔·分钟-1,P<0.01),同时钠和锂的排泄分数也显著增加。哌唑嗪未改变肾小球滤过率和有效肾血浆流量。哌唑嗪预处理未改变对呋塞米治疗(平均剂量85±14毫克)的任何肾反应。本研究表明,低剂量非降压剂量的哌唑嗪对充血性心力衰竭患者有明显的利钠作用,这主要是通过干扰肾小管重吸收实现的。