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肾素活性和血管紧张素原在大鼠脑内的分布。饮食中氯化钠摄入量对脑肾素的影响。

Distribution of renin activity and angiotensinogen in rat brain. Effects of dietary sodium chloride intake on brain renin.

作者信息

Genain C P, Van Loon G R, Kotchen T A

出版信息

J Clin Invest. 1985 Nov;76(5):1939-45. doi: 10.1172/JCI112191.

Abstract

The purpose of this study was to investigate the biochemistry and the regulation of the brain renin-angiotensin system in the Sprague-Dawley rat. Renin activity and angiotensinogen concentrations (direct and indirect radioimmunoassays) were measured in several brain areas and in neuroendocrine glands. Regional renin activities were measured in separate groups of rats on high and low NaCl diets. Mean tissue renin activities ranged from 2.2 +/- 0.6 to 54.4 +/- 19.7 fmol/mg protein per h (mean of 7 +/- SD), with the highest amounts in pineal, pituitary, and pons-medulla. NaCl depletion increased renin activity in selected regions; based on estimates of residual plasma contamination (despite perfusion of brains with saline), increased renin activity of pineal gland and posterior pituitary was attributed to higher plasma renin. To eliminate contamination by plasma renin, 16-h-nephrectomized rats were also studied. In anephric rats, NaCl depletion increased renin activity by 92% in olfactory bulbs and by 97% in anterior pituitary compared with NaCl-replete state. These elevations could not be accounted for by hyperreninemia. Brain renin activity was low and was unaffected by dietary NaCl in amygdala, hypothalamus, striatum, frontal cortex, and cerebellum. In contrast to renin, highest angiotensinogen concentrations were measured in hypothalamus and cerebellum. Overall, angiotensinogen measurements with the direct and the indirect assays were highly correlated (n = 56, r = 0.96, P less than 0.001). We conclude that (a) NaCl deprivation increases renin in olfactory bulbs and anterior pituitary of the rat, unrelated to contamination by plasma renin; and (b) the existence of angiotensinogen, the precursor of angiotensins, is demonstrated by direct radioimmunoassay throughout the brain and in neuroendocrine glands.

摘要

本研究的目的是调查Sprague-Dawley大鼠脑肾素-血管紧张素系统的生物化学及调节机制。在几个脑区和神经内分泌腺中测量了肾素活性和血管紧张素原浓度(直接和间接放射免疫测定法)。在高盐和低盐饮食的不同组大鼠中测量了区域肾素活性。组织平均肾素活性范围为每小时2.2±0.6至54.4±19.7 fmol/mg蛋白质(平均7±标准差),松果体、垂体和脑桥-延髓中的含量最高。氯化钠缺乏会增加特定区域的肾素活性;基于对残余血浆污染的估计(尽管用盐水灌注大脑),松果体和垂体后叶肾素活性的增加归因于血浆肾素水平升高。为了消除血浆肾素的污染,还对切除肾脏16小时的大鼠进行了研究。在无肾大鼠中,与氯化钠充足状态相比,氯化钠缺乏使嗅球中的肾素活性增加92%,垂体前叶中的肾素活性增加97%。这些升高不能用高肾素血症来解释。杏仁核、下丘脑、纹状体、额叶皮质和小脑中的脑肾素活性较低,且不受饮食中氯化钠的影响。与肾素相反,下丘脑和小脑中测量到的血管紧张素原浓度最高。总体而言,直接和间接测定法测量的血管紧张素原高度相关(n = 56,r = 0.96,P < 0.001)。我们得出结论:(a)氯化钠缺乏会增加大鼠嗅球和垂体前叶中的肾素,与血浆肾素污染无关;(b)通过直接放射免疫测定法证明,血管紧张素的前体血管紧张素原存在于整个大脑和神经内分泌腺中。

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