van Paassen P, de Zeeuw D, Navis G, de Jong P E
Groningen Institute for Drug Studies (of Gronigen Utrecht Institute for Drug Exploration), Department of Medicine, State University Hospital, Netherlands.
Hypertension. 1996 Feb;27(2):202-8. doi: 10.1161/01.hyp.27.2.202.
Many patients with essential hypertension respond to a high dietary sodium intake with a rise in blood pressure. Experimental evidence suggests that the renal hemodynamic response to sodium determines, at least partially, this rise in blood pressure. Our aim was to clarify the role of the renin-angiotensin system in the renal and systemic adaptation to a change in dietary sodium. We studied changes in mean arterial pressure (MAP) (millimeters of mercury), effective renal plasma flow (ERPF), body weight, and immunoreactive renin in 17 patients with essential hypertension and 15 normotensive control subjects, randomly crossing over between a 3-week sodium-restricted (50 mmol/24 h) and a sodium-replete (200 mmol/24 h) diet period. In addition, the effects of renin inhibition by remikiren (600 mg, single oral dose) were studied during the high sodium period. In normotensive control subjects, high sodium intake had no effect on MAP or body weight, whereas ERPF increased (490 +/- 19 to 535 +/- 21 mL/min, P < .05) and immunoreactive renin decreased (32 +/- 6 to 14 +/- 1 pg/mL). In hypertensive subjects, high sodium intake induced a heterogeneous response of MAP (median change, 2.6 mm Hg; range, -4.7 to +21.2; P = NS) and ERPF (median change, 21 mL/min; range, -33 to +98; P = NS). Body weight increased from 81.3 +/- 1.9 to 82.5 +/- 2.0 kg (P < .05), and immunoreactive renin decreased from 18 +/- 3 to 10 +/- 1 pg/mL (P < .05). Interestingly, the patients with a distinct rise in MAP showed a blunted ERPF response to high sodium intake (r = -.70, P < .01) and an increase in body weight (r = .76, P < .001). Moreover, the increase of ERPF was more pronounced in patients with a larger fall in immunoreactive renin (r = .77, P < .001). After administration of remikiren, a heterogeneous response in ERPF was observed: the patients with the blunted ERPF response to high sodium intake showed the largest ERPF rise (r = .70, P < .01). The remikiren-induced rise in ERPF correlated (r = .68, P < .01) with the fall in MAP (114 +/- 2 to 110 +/- 2 mm Hg). In conclusion, in patients with essential hypertension a rise in blood pressure in response to high sodium intake appears to partially be the result of insufficient renal vasodilatation. This seems to be due to an inadequate (intrarenal?) renin-angiotensin system response to increased sodium intake.
许多原发性高血压患者对高钠饮食摄入的反应是血压升高。实验证据表明，肾脏对钠的血流动力学反应至少部分地决定了这种血压升高。我们的目的是阐明肾素 - 血管紧张素系统在肾脏和全身对饮食钠变化的适应性中的作用。我们研究了17例原发性高血压患者和15例血压正常的对照受试者在3周钠限制（50 mmol/24 h）和钠充足（200 mmol/24 h）饮食期之间随机交叉时平均动脉压（MAP）（毫米汞柱）、有效肾血浆流量（ERPF）、体重和免疫反应性肾素的变化。此外，在高钠期研究了瑞米吉仑（600 mg，单次口服剂量）抑制肾素的作用。在血压正常的对照受试者中，高钠摄入对MAP或体重无影响，而ERPF增加（490±19至535±21 mL/min，P<.05）且免疫反应性肾素降低（32±6至14±1 pg/mL）。在高血压受试者中，高钠摄入引起MAP的异质性反应（中位数变化，2.6 mmHg；范围，-4.7至+21.2；P = NS）和ERPF的异质性反应（中位数变化，21 mL/min；范围，-33至+98；P = NS）。体重从81.3±1.9增加到82.5±2.0 kg（P<.05），免疫反应性肾素从18±3降低到10±1 pg/mL（P<.05）。有趣的是，MAP明显升高的患者对高钠摄入的ERPF反应迟钝（r = -.70，P<.01）且体重增加（r = .76，P<.001）。此外，免疫反应性肾素下降幅度较大的患者ERPF的增加更明显（r = .77，P<.001）。给予瑞米吉仑后，观察到ERPF的异质性反应：对高钠摄入的ERPF反应迟钝的患者ERPF升高最大（r = .70，P<.01）。瑞米吉仑诱导的ERPF升高与MAP的下降相关（r = .68，P<.01）（从114±2降至110±2 mmHg）。总之，在原发性高血压患者中，对高钠摄入的血压升高似乎部分是肾血管舒张不足的结果。这似乎是由于肾素 - 血管紧张素系统对钠摄入增加的反应不足（肾内？）。
