Hilgenfeldt U, Puschner T, Riester U, Finsterle J, Hilgenfeldt J, Ritz E
Department of Pharmaceutical Pharmacology, University of Heidelberg, Bad Kissingen, Germany.
Am J Physiol. 1998 Jul;275(1):F88-93. doi: 10.1152/ajprenal.1998.275.1.F88.
The kallikrein-kinin system (KKS) is involved in the regulation of blood pressure and in the sodium and water excretion. In humans, the KKS is divided functionally into a plasma KKS (pKKS) generating the biologically active peptide bradykinin and into the tissue (glandular) KKS (tKKS) generating the active peptide kallidin. The objective of this study was to examine the effect of a low-NaCl diet on the concentration of both pKKS and tKKS in plasma and urine in 10 healthy volunteers. After a 4-day low-NaCl diet, the urinary sodium and chloride excretions had decreased from 234 to 21.2 mmol/24 h and from 198 to 14.6 mmol/24 h, respectively. The plasma levels of ANG I, aldosterone, and angiotensin converting enzyme (ACE) significantly increased from 50.4 to 82.8 pg/ml, from 129 to 315 pg/ml, and from 46.4 to 59.8 U/ml, respectively, demonstrating the physiological adjustment to the low-salt diet. In plasma, the levels of bradykinin and plasma kallikrein had significantly decreased from 13.7 to 7.57 pg/ml and 14.4 to 7.13 U/ml, respectively. However, the levels of high-molecular-weight kininogen (HMW kininogen) remain unchanged (101 vs. 112 microg/ml, not significant). Contrary to plasma kallikrein, the plasma levels of tissue kallikrein increased (0.345 vs. 0.500 U/ml; P < 0.01). The plasma kallidin levels, however, did not change (64.7 vs. 68.6 pg/ml, not significant). This can be explained by a simultaneous decrease in the plasma low-molecular-weight kininogen (LMW kininogen) levels (89.9 vs. 44.4 microg/ml; P < 0.05). As in plasma, we find increased urinary concentrations of renal (tissue) kallikrein (23.3 to 42.8 U/24 h; P < 0.05) that contrast with, and are presumably counterbalanced by, urinary LMW kininogen levels (77.0 vs. 51.8 microg/24 h; P < 0.05). Consequently, in urine low-NaCl diet caused no significant change in either bradykinin or kallidin (9.2 vs. 10.8 microg/24 h, and 10.9 vs. 10.3 microg/24 h). It is concluded that the stimulation of the renin-angiotensin system on a low-NaCl diet is associated with a decrease in pKKS (bradykinin and plasma kallikrein) but not in tissue and renal KKS. Although tissue kallikrein is increased, there is no change in kallidin, as LMW kininogen in plasma and urine is decreased. These data suggest a difference in the regulation of pKKS and tKKS by low-salt diet.
激肽释放酶 - 激肽系统（KKS）参与血压调节以及钠和水的排泄。在人类中，KKS在功能上分为产生生物活性肽缓激肽的血浆KKS（pKKS）和产生活性肽胰激肽的组织（腺体）KKS（tKKS）。本研究的目的是检测低氯化钠饮食对10名健康志愿者血浆和尿液中pKKS和tKKS浓度的影响。经过4天的低氯化钠饮食后，尿钠和氯排泄量分别从234降至21.2 mmol/24小时和从198降至14.6 mmol/24小时。血管紧张素I（ANG I）、醛固酮和血管紧张素转换酶（ACE）的血浆水平分别从50.4显著升高至82.8 pg/ml、从129升高至315 pg/ml和从46.4升高至59.8 U/ml，表明对低盐饮食的生理调节。在血浆中，缓激肽和血浆激肽释放酶水平分别从13.7显著降至7.57 pg/ml和从14.4降至7.13 U/ml。然而，高分子量激肽原（HMW激肽原）水平保持不变（101对112μg/ml，无显著差异）。与血浆激肽释放酶相反，组织激肽释放酶的血浆水平升高（0.345对0.500 U/ml；P < 0.01）。然而，血浆胰激肽水平没有变化（64.7对68.6 pg/ml，无显著差异）。这可以通过血浆低分子量激肽原（LMW激肽原）水平同时降低来解释（89.9对44.4μg/ml；P < 0.05）。与血浆情况一样，我们发现肾脏（组织）激肽释放酶的尿浓度升高（23.3至42.8 U/24小时；P < 0.05），这与尿LMW激肽原水平（77.0对51.8μg/24小时；P < 0.05）形成对比，并且可能相互抵消。因此，在尿液中，低氯化钠饮食对缓激肽或胰激肽均未引起显著变化（9.2对10.8μg/24小时，以及10.9对10.3μg/24小时）。得出的结论是，低氯化钠饮食对肾素 - 血管紧张素系统的刺激与pKKS（缓激肽和血浆激肽释放酶）的降低有关，但与组织和肾脏KKS无关。尽管组织激肽释放酶增加，但胰激肽没有变化，因为血浆和尿液中的LMW激肽原减少。这些数据表明低盐饮食对pKKS和tKKS的调节存在差异。
