Van de Kar L D, Urban J H, Brownfield M S, Simmons W H
Hypertension. 1987 Jun;9(6):598-606. doi: 10.1161/01.hyp.9.6.598.
Previous studies have indicated that administration of the serotonin releaser p-chloroamphetamine HCl produces a dose-dependent increase in renin secretion through a blood-borne renin-releasing factor. The present studies were designed to partially characterize this renin-releasing factor using an in vitro kidney slice method for the bioassay of renin-releasing activity. Plasma from p-chloroamphetamine-treated, nephrectomized rats was used to obtain the renin-releasing factor, which was fractionated by ultrafiltration into fractions of molecular weight ranges of 1000 to 5000, 5000 to 10,000, and 10,000 to 20,000. The molecular weight ranges of the renin-releasing factor was determined to be between 5000 and 10,000. Since previous studies have shown that lesions in the hypothalamus prevent the effect of p-chloroamphetamine on renin secretion, we tested whether a hypothalamic extract can release renin from kidney slices. Addition of extracts of boiled rat hypothalamic tissue to the kidney slices caused an increase in renin release. Addition of cerebellar extracts produced a smaller increase in renin release, whereas addition of pituitary extracts had no effect. Fractionation by ultrafiltration of bovine hypothalamic extract revealed that the fraction with a molecular weight range of 5000 to 10,000 possessed the highest renin-releasing ability. The 1000 to 5000 (molecular weight) fraction possessed a sizeable renin-releasing activity, but the 10,000 to 20,000 fraction had no renin-releasing activity. Both bovine hypothalamus fractions (molecular weights between 1000-5000 and 5000-10,000) and plasma fraction lost their renin-releasing activity after digestion with pronase, suggesting that the renin-releasing factor or factors are peptides. These results suggest that a renin-releasing factor originate in the hypothalamus.
先前的研究表明，给予血清素释放剂盐酸对氯苯丙胺会通过一种血源性肾素释放因子使肾素分泌呈剂量依赖性增加。本研究旨在使用体外肾切片法对这种肾素释放因子进行部分特性鉴定，以用于肾素释放活性的生物测定。用对氯苯丙胺处理过的肾切除大鼠的血浆来获取肾素释放因子，通过超滤将其分离成分子量范围为1000至5000、5000至10000以及10000至20000的级分。肾素释放因子的分子量范围被确定为在5000至10000之间。由于先前的研究表明下丘脑损伤会阻止对氯苯丙胺对肾素分泌的影响，我们测试了下丘脑提取物是否能从肾切片中释放肾素。向肾切片中添加煮沸的大鼠下丘脑组织提取物会导致肾素释放增加。添加小脑提取物导致肾素释放的增加较小，而添加垂体提取物则没有效果。对牛下丘脑提取物进行超滤分级显示，分子量范围为5000至10000的级分具有最高的肾素释放能力。分子量为1000至5000的级分具有相当大的肾素释放活性，但分子量为10000至20000的级分没有肾素释放活性。牛下丘脑的两个级分（分子量在1000 - 5000和5000 - 10000之间）以及血浆级分在用链霉蛋白酶消化后均失去了它们的肾素释放活性，这表明肾素释放因子是一种或多种肽。这些结果表明一种肾素释放因子起源于下丘脑。
