Holland O B, Chud J M, Braunstein H
J Clin Invest. 1980 Feb;65(2):347-56. doi: 10.1172/JCI109678.
Urinary kallikrein excretion has been reported to be decreased in patients with essential hypertension and elevated in patients with primary aldosteronism as a reflection of mineralocorticoid activity. Low renin essential hypertension (LREH) has been postulated to result from excess production of an unknown mineralocorticoid(s). Urinary kallikrein excretion was compared in outpatients with essential hypertension, mineralocorticoid hypertension (primary aldosteronism and 17alpha-hydroxylase deficiency), and in normal subjects of the same race. No significant difference in urinary kallikrein excretion of patients with LREH vs. normal renin essential hypertension (NREH) was found for either black (4.1+/-0.4 vs. 4.8+/-0.5 esterase units (EU)/24 h, mean+/-SE, for 27 LREH and 38 NREH, respectively) or white patients (12.2+/-2.3 vs. 11.7+/-1.4 EU/24 h for 13 LREH and 25 NREH, respectively). Urinary kallikrein was decreased in black vs. white hypertensive patients and normal subjects. However, in patients with normal renal function (creatinine clearance >/=80 ml/min) urinary kallikrein was not significantly decreased in either black hypertensive vs. black normal subjects (4.3+/-0.3 vs. 5.4+/-0.6 EU/24 h) or in white hypertensive vs. white normal subjects (11.9+/-1.2 vs. 8.4+/-0.9 EU/24 h). In contrast, hypertensive patients with mild renal insufficiency (creatinine clearance of 41.8+/-78.5 ml/min) had reduced (P < 0.05) urinary kallikrein (3.3 EU/24 h with creatinine clearance of 63.6+/-2.0 for 24 black patients and 4.2+/-0.7 EU/24 h with creatinine clearance of 67.0+/-3.5 for 6 white patients). These results suggest that a reduction in urinary kallikrein excretion rate is an early accompaniment of hypertensive renal injury. Urinary kallikrein excretion in response to a 6-d 10-meq sodium diet and a 3-d Florinef (0.5 mg b.i.d.) administration was compared in hypertensive patients with normal renal function vs. race and age-matched normal subjects. Stimulation of urinary kallikrein excretion by Florinef was equal in black and white normal subjects vs. hypertensive patients (black normals = 12.3+/-2.7 [n = 9], NREH = 11.7+/-1.8 [n = 10], LREH = 10.9+/-1.5 [n = 12]; white normals = 21.2+/-2.9 [n = 11], essential hypertension = 20.9+/-3.2 [10 NREH, 5 LREH]). Stimulation of urinary kallikrein excretion with low sodium diet was decreased (P < 0.05) only in black LREH (black normals = 11.2+/-2.4 [n = 10], NREH = 10.1+/-2.7 [n = 10], LREH = 7.4+/-1.1 [n = 13]; white normals = 19.1+/-2.7 [n = 13], essential hypertension = 17.5+/-2.3 [nine NREH, four LREH]). However, during low sodium diet, black patients with LREH had evidence for less sodium depletion as manifested by a decreased rise in urinary aldosterone excretion (16.3+/-2.7 vs. 33.3+/-6.4 mug/24 h for black normals) and a failure to achieve metabolic balance in 11/13 patients. Thus, the lesser kallikrein stimulation appeared to result from these two factors. Black and white hypertensives with creatinine clearance <80 ml/min had little increase in urinary kallikrein excretion with Florinef or low sodium diet.5 of 12 patients with primary aldosteronism or 17alpha-hydroxylase deficiency did not have an elevated urinary kallikrein excretion rate. Mild renal insufficiency may have contributed to this finding in two of these five patients. Nevertheless, this finding illustrates a limitation to the use of urinary kallikrein excretion rate as an index of mineralocorticoid activity. However, it appears that the majority of patients with LREH have no evidence for excess production of an unknown mineralocorticoid. The failure to find a decrease in urinary kallikrein excretion in racially matched patients with essentil hypertension and normal renal function questions the postulate of a role of the kallikrein-kinin system in the initiation of essential hypertension.
据报道，原发性高血压患者的尿激肽释放酶排泄量减少，而原发性醛固酮增多症患者的尿激肽释放酶排泄量升高，这反映了盐皮质激素的活性。低肾素性原发性高血压（LREH）被推测是由一种未知盐皮质激素的过量产生所致。对原发性高血压、盐皮质激素性高血压（原发性醛固酮增多症和17α-羟化酶缺乏症）门诊患者以及同种族正常受试者的尿激肽释放酶排泄情况进行了比较。无论是黑人（27例LREH患者和38例正常肾素性原发性高血压（NREH）患者，分别为4.1±0.4和4.8±0.5酯酶单位（EU）/24小时，均值±标准误）还是白人患者（13例LREH患者和25例NREH患者，分别为12.2±2.3和11.7±1.4 EU/24小时），LREH患者与NREH患者的尿激肽释放酶排泄均无显著差异。黑人高血压患者和白人高血压患者以及正常受试者的尿激肽释放酶排泄量均低于白人。然而，在肾功能正常（肌酐清除率≥80 ml/分钟）的患者中，无论是黑人高血压患者与黑人正常受试者（4.3±0.3与5.4±0.6 EU/24小时）还是白人高血压患者与白人正常受试者（11.9±1.2与8.4±0.9 EU/24小时），尿激肽释放酶排泄均无显著降低。相比之下，轻度肾功能不全（肌酐清除率为41.8±78.5 ml/分钟）的高血压患者尿激肽释放酶排泄减少（P<0.05）（24例黑人患者肌酐清除率为63.6±2.0时为3.3 EU/24小时，6例白人患者肌酐清除率为67.0±3.5时为4.2±0.7 EU/24小时）。这些结果表明，尿激肽释放酶排泄率降低是高血压肾损伤的早期伴随症状。对肾功能正常的高血压患者与种族和年龄匹配的正常受试者进行比较，观察其在6天10毫当量钠饮食和3天氟氢可的松（0.5毫克，每日两次）给药后尿激肽释放酶的排泄情况。氟氢可的松对黑人正常受试者和白人正常受试者尿激肽释放酶排泄的刺激作用与高血压患者相同（黑人正常受试者=12.3±2.7 [n=9]，NREH=11.7±1.8 [n=10]，LREH=10.9±1.5 [n=12]；白人正常受试者=21.2±2.9 [n=11]，原发性高血压=20.9±3.2 [10例NREH，5例LREH]）。仅在黑人LREH患者中，低钠饮食对尿激肽释放酶排泄的刺激作用降低（P<0.05）（黑人正常受试者=11.2±2.4 [n=10]，NREH=10.1±2.7 [n=10]，LREH=7.4±1.1 [n=13]；白人正常受试者=19.1±2.7 [n=13]，原发性高血压=17.5±2.3 [9例NREH，4例LREH]）。然而，在低钠饮食期间，LREH黑人患者的钠耗竭证据较少，表现为尿醛固酮排泄增加减少（黑人正常受试者为16.3±2.7与33.3±6.4微克/24小时），且13例患者中有11例未达到代谢平衡。因此，激肽释放酶刺激作用较小似乎是由这两个因素导致的。肌酐清除率<80 ml/分钟的黑人和白人高血压患者，氟氢可的松或低钠饮食对其尿激肽释放酶排泄的增加作用较小。12例原发性醛固酮增多症或17α-羟化酶缺乏症患者中有5例尿激肽释放酶排泄率未升高。其中5例患者中有2例轻度肾功能不全可能导致了这一结果。尽管如此，这一发现说明了将尿激肽释放酶排泄率用作盐皮质激素活性指标的局限性。然而，似乎大多数LREH患者并无证据表明存在未知盐皮质激素的过量产生。在种族匹配、肾功能正常的原发性高血压患者中未发现尿激肽释放酶排泄减少，这对激肽释放酶-激肽系统在原发性高血压发病中起作用的假设提出了质疑。
