氯噻酮、螺内酯和普萘洛尔治疗正常肾素性原发性高血压的患者内比较

Intrapatient comparison of treatment with chlorthalidone, spironolactone and propranolol in normoreninemic essential hypertension.

作者信息

Drayer J I, Kloppenborg P W, Festen J, van't Laar A, Benraad T J

出版信息

Am J Cardiol. 1975 Oct 31;36(5):716-21. doi: 10.1016/0002-9149(75)90174-5.

Abstract

The effects of chlorthalidone, spironolactone and propranolol in reducing blood pressure were compared in the same 11 normoreninemic hypertensive patients. All three drugs decreased the blood pressure significantly and no agent had a superior blood pressure-lowering effect. The blood pressure did not normalize. The data suggest that no one variable--volume factors, relative hyperactivity of the renin-aldosterone system or beta-adrenergic hyperactivity--is the prime mover in normoreninemic hypertension. Long-term treatment with chlorthalidone resulted in slight hyperreninism (26.3 +/- 4.9 ng-ml-1-3 hours-1) (mean +/- standard error) with concomitant changes in plasma aldosterone (23.0 +/- 3.2 ng-100 ml-1). The body weight decreased significantly (--1.8 kg, P less than 0.005). Plasma potassium concentrations were low (3.2 +/- 0.1 mEq-liter -1). Creatinine clearance was unimpaired (117 +/- 6 ml-min-1). Treatment with spironolactone resulted in more marked hyperreninism (47.0 +/- 14.3 ng-ml-1-3 hours-1) and hyperaldosteronism (61.9 +/-11.8 ng-100 ml-1). The body weight decreased significantly (--1.9 kg, P less than 0.004). Significant hyperkalemia occurred (4.4 +/- 0.1 mEq-liter-1). The glomerular filtration rate decreased significantly to 93 +/- 3 ml-min-1 (P less than 0.004). Treatment with propranolol resulted in marked suppression of the plasma renin activity (1.8 +/- 0.2 ng-ml-1-3 hours-1) and plasma aldosterone levels (8.9 +/- 1.3 ng-100 ml-1). A significant increase in body weight occurred (+2.3 kg, P less than 0.013). The plasma potassium concentration increased to a level not significantly different from the value found after treatment with spironolactone (4.2 +/- 0.1 mEq-liter-1). The creatinine clearance decreased significantly to 99 +/- 5 ml-min-1 (P less than 0.008). Hyperreninemia (by spironolactone and chlorthalidone), effective hyperaldosteronism (by chlorthalidone) and volume retention (by propranolol) are considered to represent expressions of mechanisms counteracting the depressor effects of these different pharmacologic maneuvers, leading to the maintenance of supranormal blood pressure.

摘要

在11名正常肾素性高血压患者中比较了氯噻酮、螺内酯和普萘洛尔的降压效果。所有三种药物均显著降低血压，且没有一种药物具有更优的降压效果。血压未恢复正常。数据表明，在正常肾素性高血压中，没有一个变量——容量因素、肾素 - 醛固酮系统相对亢进或β - 肾上腺素能亢进——是主要驱动因素。长期使用氯噻酮治疗导致轻度高肾素血症（26.3±4.9 ng·ml⁻¹·3小时⁻¹）（均值±标准误），同时血浆醛固酮发生变化（23.0±3.2 ng·100 ml⁻¹）。体重显著下降（-1.8 kg，P<0.005）。血浆钾浓度较低（3.2±0.1 mEq·升⁻¹）。肌酐清除率未受影响（117±6 ml·分钟⁻¹）。使用螺内酯治疗导致更明显的高肾素血症（47.0±14.3 ng·ml⁻¹·3小时⁻¹）和高醛固酮血症（61.9±11.8 ng·100 ml⁻¹）。体重显著下降（-1.9 kg，P<0.004）。出现显著高钾血症（4.4±0.1 mEq·升⁻¹）。肾小球滤过率显著降至93±3 ml·分钟⁻¹（P<0.004）。使用普萘洛尔治疗导致血浆肾素活性（1.8±0.2 ng·ml⁻¹·3小时⁻¹）和血浆醛固酮水平（8.9±1.3 ng·100 ml⁻¹）显著受到抑制。体重显著增加（+2.3 kg，P<0.013）。血浆钾浓度升高至与使用螺内酯治疗后的值无显著差异的水平（4.2±0.1 mEq·升⁻¹）。肌酐清除率显著降至99±5 ml·分钟⁻¹（P<0.008）。高肾素血症（由螺内酯和氯噻酮引起）、有效高醛固酮血症（由氯噻酮引起）和容量潴留（由普萘洛尔引起）被认为是对抗这些不同药理操作降压作用的机制表现，导致维持高于正常的血压。