van Paassen P, Navis G J, De Jong P E, De Zeeuw D
Department of Medicine, State University, Groningen, the Netherlands.
Eur J Clin Invest. 1999 Dec;29(12):1019-26. doi: 10.1046/j.1365-2362.1999.00573.x.
In essential hypertension an elevated renal vascular resistance (RVR) may be a marker of renin-angiotensin-aldosterone system-mediated impairment of renal sodium excretion. This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic response to specific renin-angiotensin-aldosterone system (RAAS) blockade by renin-inhibitor remikiren could be predicted from pretreatment renal vascular tone.
Renal hemodynamics, and the effects of single (n = 17) and multiple doses (n = 8, 8 days) of remikiren (600 mg day-1) on sodium excretion were studied under conditions of carefully controlled sodium balance.
Pretreatment renal vascular tone showed considerable individual differences: filtration fraction (FF) ranged from 21.2 to 30.3% and RVR from 18.8 to 33.5 10-2 mmHg min mL-1 in the single dose study, and FF from 20.8 to 24.9% and RVR from 14.8 to 28.8 10-2 mmHg min mL-1 in the multiple dose study. Remikiren induced a fall in blood pressure, FF and RVR, with considerable interindividual variability in natriuretic response. During single dose, cumulative sodium loss was 5.1 mmol per 5 h (-8.8 to +24.6), whereas after 8 days treatment cumulative sodium loss was 72 +/- 30 mmol (-46 to +187). The natriuretic response to remikiren during single as well as multiple dose significantly correlated with pretreatment renal vascular tone (estimated from FF and RVR) but not with remikiren-induced changes in renal hemodynamics or in hormonal parameters. Cumulative sodium loss was largest in patients with a higher pretreatment FF and RVR (r = 0.74, P < 0.001 and r = 0.52, P < 0.05, respectively, single dose; and r = 0.75, P < 0.05 and r = 0.73, P < 0.05, respectively, multiple dose).
These data support the hypothesis that in essential hypertension an elevated renal vascular tone is a marker of RAAS-mediated impairment of sodium excretion.
在原发性高血压中，肾血管阻力（RVR）升高可能是肾素 - 血管紧张素 - 醛固酮系统介导的肾钠排泄受损的一个标志。通过研究在原发性高血压患者中，能否根据治疗前的肾血管张力来预测肾素抑制剂瑞米吉仑对特定肾素 - 血管紧张素 - 醛固酮系统（RAAS）的阻断作用所产生的利钠反应，对这一假设进行了验证。
在严格控制钠平衡的条件下，研究了肾血流动力学以及单次（n = 17）和多次剂量（n = 8，8天）瑞米吉仑（600毫克/天）对钠排泄的影响。
治疗前肾血管张力存在相当大的个体差异：在单次剂量研究中，滤过分数（FF）范围为21.2%至30.3%，RVR范围为18.8至33.5×10⁻² mmHg·min·mL⁻¹；在多次剂量研究中，FF范围为20.8%至24.9%，RVR范围为14.8至28.8×10⁻² mmHg·min·mL⁻¹。瑞米吉仑可使血压、FF和RVR下降，利钠反应存在相当大的个体间变异性。在单次剂量期间，每5小时累积钠丢失量为5.1 mmol（-8.8至+24.6），而在治疗8天后，累积钠丢失量为72±30 mmol（-46至+187）。单次及多次剂量时瑞米吉仑的利钠反应与治疗前肾血管张力（根据FF和RVR估算）显著相关，但与瑞米吉仑引起的肾血流动力学或激素参数变化无关。治疗前FF和RVR较高的患者累积钠丢失量最大（单次剂量时，r分别为0.74，P < 0.001和r = 0.52，P < 0.05；多次剂量时，r分别为0.75，P < 0.05和r = 0.73，P < 0.05）。
这些数据支持了以下假设，即在原发性高血压中，肾血管张力升高是RAAS介导的钠排泄受损的一个标志。
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