Bellini C, Ferri C, Carlomagno A, Necozione S, Lepore A R, Desideri G, Santucci A
Department of Experimental Medicine, University of L'Aquila, Italy.
J Am Soc Nephrol. 1996 Dec;7(12):2565-77. doi: 10.1681/ASN.V7122565.
Active and inactive urinary kallikrein excretion rates were evaluated in 43 essential hypertensive men (45.4 +/- 5.6 yr) after normal-(120 mmol/day), low-(20 mmol/day), and high-(240 mmol/day) NaCl diets were given for 2 wk each. Patients were classified as salt-sensitive, salt-resistant, or counterregulating, on the basis of their blood pressure responses to the different NaCl intakes. Resulting data show that active and inactive kallikrein excretion rates were lower (P < 0.001) in salt-sensitive (active, 0.59 +/- 0.27 U/24 h; inactive, 3.45 +/- 1.31 U/24 h) than in salt-resistant (active, 1.41 +/- 0.35 U/24 h; inactive, 6.93 +/- 2.68 U/24 h) and in counterregulating hypertensive patients (active, 1.37 +/- 0.39 U/24 h; inactive, 6.32 +/- 2.58 U/24 h) after the normal NaCl diet. Salt-sensitive hypertensive patients showed also higher plasma digoxin-like substance (P < 0.001), atrial natriuretic peptide (P < 0.001), and fasting insulin (P < 0.005) levels than the other subgroups. Active kallikrein decreased after high and increased after low-NaCl intake in all groups. Inactive kallikrein varied similarly to active one in salt-resistant patients and counterregulating patients, whereas it increased during salt-loading in salt-sensitive patients. Consequently, the active/total kallikrein ratio decreased in salt-sensitive patients (from 20.2 +/- 3.5 to 5.82 +/- 1.02%, P < 0.05) when they switched from low- to high-NaCl intake, and the ratio was lower in these patients than in the other subgroups (P < 0.0001) after the high-NaCl diet. In conclusion, active and inactive kallikrein excretions after normal-NaCl intake are reduced in salt-sensitive hypertensive patients. The divergent active and inactive kallikrein responses to dietary NaCl changes in salt-sensitive patients could indicate an impairment of inactive to active kallikrein conversion during NaCl loading as a new mechanism in human salt-sensitive hypertension.
对43名原发性高血压男性患者（45.4±5.6岁）分别给予正常（120mmol/天）、低（20mmol/天）和高（240mmol/天）盐饮食，每种饮食持续2周，然后评估其活性和非活性尿激肽释放酶排泄率。根据患者对不同氯化钠摄入量的血压反应，将其分为盐敏感型、盐抵抗型或反调节型。结果显示，盐敏感型患者（活性，0.59±0.27U/24小时；非活性，3.45±1.31U/24小时）的活性和非活性激肽释放酶排泄率低于盐抵抗型患者（活性，1.41±0.35U/24小时；非活性，6.93±2.68U/24小时）和反调节型高血压患者（活性，1.37±0.39U/24小时；非活性，6.32±2.58U/24小时）（P<0.001）。正常氯化钠饮食后，盐敏感型高血压患者的血浆地高辛样物质（P<0.001）、心房利钠肽（P<0.001）和空腹胰岛素（P<0.005）水平也高于其他亚组。所有组中，高盐摄入后活性激肽释放酶减少，低盐摄入后活性激肽释放酶增加。在盐抵抗型患者和反调节型患者中，非活性激肽释放酶的变化与活性激肽释放酶相似，而在盐敏感型患者中，盐负荷期间非活性激肽释放酶增加。因此，盐敏感型患者从低盐摄入改为高盐摄入时，活性/总激肽释放酶比值降低（从20.2±3.5降至5.82±1.02%，P<0.05），高盐饮食后这些患者的该比值低于其他亚组（P<0.0001）。总之，盐敏感型高血压患者正常氯化钠摄入后的活性和非活性激肽释放酶排泄减少。盐敏感型患者中活性和非活性激肽释放酶对饮食中氯化钠变化的不同反应可能表明，在氯化钠负荷期间非活性激肽释放酶向活性激肽释放酶的转化受损，这是人类盐敏感型高血压的一种新机制。
