Defect in the sodium-modulated tissue responsiveness to angiotensin II in essential hypertension.
Defect in the sodium-modulated tissue responsiveness to angiotensin II in essential hypertension.
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DOI：
10.1172/jci111176
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发表时间：
1983-12
期刊：
影响因子：
--
通讯作者：
D. Shoback;G. Williams;T. Moore;R. Dluhy;S. Podolsky;N. Hollenberg
中科院分区：
文献类型：
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作者：
D. Shoback;G. Williams;T. Moore;R. Dluhy;S. Podolsky;N. Hollenberg
在正常受试者中，膳食钠摄入量可调节肾血管、肾上腺和对输注血管紧张素 II (AII) 的升压反应。为了检验这种调节在某些原发性高血压患者中异常的假设，我们对 18 名高血压患者和 9 名正常受试者进行了两次研究——在饮食限制钠期间和负荷期间。对氨基马尿酸（PAH）清除率用于评估肾血浆流量。 AII 以分级剂量输注（0.3-3.0 ng/kg/min）。在每次 AII 剂量开始和结束时测量血浆醛固酮、皮质醇、肾素活性、AII、钠、钾和 PAH 清除率。在饮食补充钠期间，八名原发性高血压受试者对 AII 输注（每分钟 3 ng/kg）表现出正常的肾血管反应（每 1.73 平方米大于 125 毫升/分钟）。这些正常反应者 (NR) 的肾血流量减少量为 168 +/- 10，与血压正常受试者的范围相当（每 1.73 m2 206 +/- 25 ml/min）。与 NR 和正常血压受试者相比，所有剩余的高血压患者（指定为异常反应者 (AbR)）对相同剂量的 AII 输注的肾血流反应较低（小于 125）（平均减少量：每 1.73 m2 84 +/- 11 ml/min）。在 NR（P 小于 0.001，卡方）和正常血压（P = 0.004，卡方）中，高盐饮食与低盐饮食对所有 AII 剂量的肾血流反应具有统计学意义，但钠摄入量对 AbR 中的这种反应没有影响。 NR 中的基础肾血流量随着膳食钠补充显着增加（P 小于 0.001，配对 t 检验），从每 1.73 m2 491 +/- 36（低盐）增加到 602 +/- 40 ml/min（高盐），但不同膳食钠摄入量的 AbR 几乎相同（每 1.73 m2 为 429 +/- 24 vs. 425 +/- 26 ml/min）。 1.73 平方米）。两个亚组的肾上腺对钠摄入和输注 AII 的反应也不同。在 NR 中，限制钠摄入后，肾上腺对 AII 的反应显着增强（P = 0.011，Wilcoxon 符号秩检验）。相比之下，AbR 中低钠饮食和高钠饮食之间的醛固酮对 AII 输注的反应没有显着差异。因此，原发性高血压的一个重要亚组在两个对容量稳态至关重要的系统（肾脏和肾上腺）中对 AII 的反应异常。他们无法通过改变膳食钠摄入量来调节肾血流量和醛固酮对 AII 的反应。此外，基础肾血流量不会随着钠摄入量的增加而适当增加。这些异常可能是由于这三个靶组织中 AII 局部产生增加或 AII 受体缺陷所致，可能导致血压升高。
In normal subjects, dietary sodium intake modulates renovascular, adrenal, and pressor responses to infused angiotensin II (AII). To examine the hypothesis that this modulation is abnormal in some patients with essential hypertension, we studied 18 hypertensives and 9 normal subjects twice--during dietary sodium restriction and during loading. Paraaminohippurate (PAH) clearance was used to assess renal plasma flow. AII was infused in graded doses (0.3-3.0 ng/kg per min). Plasma aldosterone, cortisol, renin activity, AII, sodium, potassium, and PAH clearance were measured at the onset and end of each AII dose. During dietary sodium repletion, eight of the subjects with essential hypertension showed a normal renovascular response (greater than 125 ml/min per 1.73 m2) to AII infusion (3 ng/kg per min). The decrement in renal blood flow in these normal responders (NR) was 168 +/- 10, which was comparable to the range in normotensive subjects (206 +/- 25 ml/min per 1.73 m2). All of the remaining hypertensive patients, designated abnormal responders (AbR), had lower (less than 125) renal blood flow responses to the same dose of infused AII (mean decrement: 84 +/- 11 ml/min per 1.73 m2) compared with the NR and normotensive subjects. Renal blood flow responses to all AII doses were statistically greater on a high-vs.-low salt diet in the NR (P less than 0.001, chi-square) and normotensives (P = 0.004, chi-square) but sodium intake had no effect on this response in the AbR. Basal renal blood flow in NR increased significantly (P less than 0.001, paired t test) with dietary sodium repletion, from 491 +/- 36 (low salt) to 602 +/- 40 ml/min per 1.73 m2 (high salt), but was almost identical in the AbR on differing dietary sodium intakes (429 +/- 24 vs. 425 +/- 26 ml/min per 1.73 m2). The adrenal responses to sodium intake and infused AII also differed in the two subgroups. In the NR, the adrenal response to AII was significantly greater (P = 0.011, Wilcoxon signed rank test) after sodium restriction. In contrast, there was no significant difference in the aldosterone response to AII infusion between the low and high sodium diets in the AbR. Thus, a substantial subgroup of essential hypertensives has an abnormality in responsiveness to AII in two systems central to volume homeostasis: the kidney and adrenal. They fail to modulate their renal blood flow and aldosterone responses to AII with changes in dietary sodium intake. Moreover, basal renal blood flow does not increase appropriately with increased sodium intake. These abnormalities, which may be due to an increased local production of AII or a defect in the AII receptors in these three target tissues, could contribute to the elevated blood pressure.