Yasujima M, Abe K, Tanno M, Kohzuki M, Omata K, Kasai Y, Sato M, Takeuchi K, Itoh S, Kanazawa M
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
J Hypertens. 1987 Dec;5(6):687-92. doi: 10.1097/00004872-198712000-00009.
To assess possible roles of the renal kallikrein-kinin system in the development of spontaneous hypertension, we determined daily excretion of urinary total and active kallikrein in 6-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats for up to 2 weeks. We also evaluated the effect of aprotinin, a reversible inhibitor of kallikrein and other serine proteases, on the development of hypertension in the 6-week-old SHR on ordinary intakes of sodium or on sodium loading with 1% NaCl for up to 2 weeks. Active kallikrein was determined by its kininogenase activity, and the generated kinins were radio-immunologically measured. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin (200 micrograms/ml). Urinary active kallikrein excretion was significantly reduced in 7-week-old SHR (1.5 +/- 0.2 microgram/day compared to 2.8 +/- 0.3 micrograms/day in WKY, P less than 0.05) and in 8-week-old SHR (1.6 +/- 0.2 microgram/day compared to 3.2 +/- 0.4 micrograms/day in WKY, P less than 0.01). Urinary total kallikrein excretion was also reduced in the 7- and 8-week-old SHR whereas the ratio of active to total kallikrein did not change. In addition, renal contents of total and active kallikrein were significantly lower in the 8-week-old SHR than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
为评估肾激肽释放酶-激肽系统在自发性高血压发展过程中可能发挥的作用,我们测定了6周龄自发性高血压大鼠(SHR)和Wistar-Kyoto(WKY)大鼠长达2周的尿总激肽释放酶和活性激肽释放酶的每日排泄量。我们还评估了抑肽酶(一种激肽释放酶和其他丝氨酸蛋白酶的可逆抑制剂)对6周龄SHR在普通钠摄入量或1%NaCl钠负荷条件下长达2周的高血压发展的影响。活性激肽释放酶通过其激肽原酶活性来测定,所产生的激肽通过放射免疫法进行测量。总激肽释放酶也通过在非活性激肽释放酶用胰蛋白酶(200微克/毫升)激活后测量激肽原酶活性来测定。7周龄SHR的尿活性激肽释放酶排泄量显著降低(1.5±0.2微克/天,而WKY为2.8±0.3微克/天,P<0.05),8周龄SHR也是如此(1.6±0.2微克/天,而WKY为3.2±0.4微克/天,P<0.01)。7周龄和8周龄SHR的尿总激肽释放酶排泄量也降低,而活性激肽释放酶与总激肽释放酶的比值没有变化。此外,8周龄SHR的肾总激肽释放酶和活性激肽释放酶含量显著低于对照组。(摘要截短至250字)