Katori M, Majima M, Hayashi I, Fujita T, Yamanaka M
Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Biol Chem. 2001 Jan;382(1):61-4. doi: 10.1515/BC.2001.010.
The role of the renal kallikrein-kinin system in the development of salt-sensitive hypertension was studied using mutant kininogen-deficient Brown-Norway Katholiek (BN-Ka) rats, which generate no kinin in their urine, and other hypertensive rat models. It was found that ingestion of a low sodium diet or infusion of NaCl in doses slightly above 0.15 M caused hypertension and sodium accumulation in erythrocytes and the cerebrospinal fluid of kininogen-deficient BN-Ka rats. Development of hypertension in the deoxycorticosterone-acetate-salt model was completely prevented by administration of a newly discovered inhibitor, ebelactone B, of carboxypeptidase Y-like exopeptidase (an urinary kininase). The urinary kallikrein excretion of spontaneously hypertensive rats was lower than that of Wistar Kyoto rats at 4 weeks of age and did not increase by administration of furosemide, a diuretic agent, although approximately 50% of the diuretic action of this agent was dependent upon the renal kallikrein-kinin system in normal rats. In conclusion, the renal kallikrein-kinin system works as a safety valve for excess sodium intake.
利用突变的激肽原缺陷型布朗挪威天主教大鼠（BN-Ka）以及其他高血压大鼠模型，研究了肾激肽释放酶-激肽系统在盐敏感性高血压发生发展中的作用。该突变大鼠尿液中不产生激肽。研究发现，给激肽原缺陷型BN-Ka大鼠喂食低钠饮食或输注剂量略高于0.15M的氯化钠，会导致其高血压以及红细胞和脑脊液中钠蓄积。一种新发现的羧肽酶Y样外肽酶（一种尿激肽酶）抑制剂埃贝内酯B的给药，完全预防了脱氧皮质酮-醋酸盐-盐模型中高血压的发生。自发性高血压大鼠在4周龄时尿激肽释放酶排泄量低于Wistar Kyoto大鼠，且给予利尿剂速尿后其排泄量并未增加，尽管在正常大鼠中该利尿剂约50%的利尿作用依赖于肾激肽释放酶-激肽系统。总之，肾激肽释放酶-激肽系统作为过量钠摄入的安全阀发挥作用。
