Leenen F H, Smith D L, Farkas R M, Boer W H, Reeves R A, Marquez-Julio A
Department of Medicine, Toronto Western Hospital, Ontario, Canada.
Am J Med. 1988 Jan 29;84(1B):76-85.
Fifteen patients with mild-to-moderate hypertension (10 with normal and five with decreased renal function) were studied after treatment with placebo and low (1 mg), intermediate (2.5 mg), and high (5.0 mg per day) doses of indapamide, each for four weeks. Six patients--five with normal renal function--were classified as nonresponders (decrease in diastolic blood pressure less than 5 mm Hg). The remaining nine patients had dose-related decreases in blood pressure. Patients with or without renal failure showed similar decreases in blood pressure. Blood pressure reduction was associated with a significant decrease in cardiac index in the responders at the highest dose, related to a decrease in left ventricular end-diastolic dimension and stroke volume, whereas heart rate did not increase. This apparent decrease in venous return was associated with a significant decrease in body weight but not plasma volume in the responders. Indapamide did not change plasma norepinephrine levels, but decreased pressor responsiveness to exogenous norepinephrine. Responders had lower initial plasma renin activity and a smaller absolute increase in plasma renin activity while receiving indapamide, whereas angiotensin II pressor responsiveness was decreased more. The results presented indicate that the blood pressure lowering effect of indapamide in the present patient population is observed with or without renal failure and is associated with a decrease in pressor reactivity. In nonresponders, compensatory mechanisms (e.g., renin) may negate the antihypertensive effect of indapamide.
对15例轻至中度高血压患者（10例肾功能正常，5例肾功能减退）进行了研究，患者接受安慰剂以及低剂量（1毫克）、中剂量（2.5毫克）和高剂量（每日5.0毫克）吲达帕胺治疗，每种剂量治疗4周。6例患者——5例肾功能正常——被归类为无反应者（舒张压下降小于5毫米汞柱）。其余9例患者血压呈剂量相关性下降。肾功能衰竭患者和非肾功能衰竭患者的血压下降情况相似。在最高剂量时，有反应者的血压降低与心脏指数显著下降有关，这与左心室舒张末期内径和每搏输出量的减少有关，而心率未增加。有反应者静脉回流的这种明显减少与体重显著下降有关，但与血浆容量无关。吲达帕胺未改变血浆去甲肾上腺素水平，但降低了对外源性去甲肾上腺素的升压反应性。有反应者初始血浆肾素活性较低，在接受吲达帕胺治疗时血浆肾素活性的绝对增加值较小，而血管紧张素II升压反应性下降更多。所呈现的结果表明，在本患者群体中，无论有无肾功能衰竭，均观察到吲达帕胺的降压作用，且与升压反应性降低有关。在无反应者中，代偿机制（如肾素）可能会抵消吲达帕胺的降压作用。
