Beretta-Piccoli C, Weidmann P, de Châtel R, Hirsch D, Reubi F C
Schweiz Med Wochenschr. 1977 Jan 29;107(4):104-15.
35 patients with benign essential hypertension were treated for 6 weeks with high doses of the mineralocorticoid-antagonist spironolactone (400 mg/day), or with the "loop-diuretic" mefruside (mean maximal dose 110 mg/day). Spironolactone caused greater reductions in blood pressure and blood volume and a more marked increase in plasma renin activity (PRA) than mefruside (p less than 0.05). It appears possible that he weaker antihypertensive effect of mefruside may relate partly to its lesser influence on circulatory volume. With both diuretics, mean decreases in blood pressure were greater in patients with low pre-therapeutic PRA than in patients with normal or high PRA. However, the diuretic-induced changes in blood pressure did not correlate with the associated variations in blood volume or PRA. Thus, the increased blood pressure sensitivity to diuretics in patients with low-renin essential hypertension did not appear to be volume or renin-dependent. Under normal conditions, the maintenance of a constant blood pressure during volume depletion may partly depend on compensatory activation of the sympathetic nervous system. Moreover, patients with low-renin essential hypertension have been found to have decreased adrenergic activity. It seems possible, therefore, that the marked blood pressure sensitivity to diuretic treatment in such patients may be the result of an impaired compensatory sympathetic response to sodium and volume depletion. Analysis of the literature suggests that the diuretic furosemide, a structural relative of mefruside, may also have less blood pressure lowering efficacy in patients with essential hypertension than the distally-acting thiazides, chlorthalidone or spironolactone. Consideration of possible differences in the blood pressure reducing potential of certain diuretics thus appears to be necessary in planning the pharmacotherapy of essential hypertension.
35例良性原发性高血压患者接受了为期6周的治疗，一组使用高剂量盐皮质激素拮抗剂螺内酯（400毫克/天），另一组使用“袢利尿剂”美夫西特（平均最大剂量110毫克/天）。与美夫西特相比，螺内酯导致血压和血容量的降低幅度更大，血浆肾素活性（PRA）的升高更为显著（p<0.05）。美夫西特较弱的降压作用可能部分与其对循环血容量的影响较小有关。使用这两种利尿剂时，治疗前PRA较低的患者血压平均下降幅度大于PRA正常或较高的患者。然而，利尿剂引起的血压变化与血容量或PRA的相关变化并无关联。因此，低肾素原发性高血压患者对利尿剂的血压敏感性增加似乎并非依赖于血容量或肾素。在正常情况下，血容量减少时维持恒定血压可能部分依赖于交感神经系统的代偿性激活。此外，已发现低肾素原发性高血压患者的肾上腺素能活性降低。因此，这类患者对利尿剂治疗的显著血压敏感性可能是对钠和血容量减少的代偿性交感反应受损的结果。对文献的分析表明，美夫西特的结构类似物利尿剂速尿在原发性高血压患者中的降压效果可能也低于作用于远曲小管的噻嗪类利尿剂、氯噻酮或螺内酯。因此，在规划原发性高血压的药物治疗时，考虑某些利尿剂在降压潜力上的可能差异似乎是必要的。
