PHYSIOLOGICAL ACTIONS OF THE RENIN-ANGIOTENSIN SYSTEM

这个项目的目的是研究生理学和病理学。 肾素-血管紧张素系统的各个方面，强调其在 循环动态平衡和发育。在过去一年的学习中 主要集中在a)1型血管紧张素II(Ang II)受体的作用 定位于小细胞促肾上腺皮质激素释放激素CRH和CRH/VP 下丘脑室旁核(PVN)中的细胞，以及b) 慢性应激对外周血肾素-血管紧张素-醛固酮的影响 系统。 A)糖皮质激素对下丘脑室旁核Ang II受体的调节 血管紧张素Ⅱ在调节下丘脑-垂体-肾上腺轴反应性中的作用 应激通过相关血管紧张素Ⅱ受体在下丘脑室旁核的表达来研究 伴随着HPA轴活动的变化。各种应激范式 血管紧张素Ⅱ受体在小细胞亚群中的表达增加 PVN以类似的方式进行，而不考虑它们对活性的影响 HPA轴的位置。血管紧张素Ⅱ受体在小细胞上的表达 肾上腺切除后减少，糖皮质激素治疗后增加。 应激对下丘脑室旁核血管紧张素Ⅱ受体表达的刺激作用 通过肾上腺切除来预防，这表明糖皮质激素 对于压力的影响是必要的。这些数据支持Ang II的作用 在适应压力的中央机制中，但表明Ang II不起控制HPA轴反应的作用。 B)反复的身体-心理压力减少了基础和刺激 尽管基础血浆肾素活性升高，但仍可分泌醛固酮。 血浆肾素活性的增加与 反复交感神经对肾脏肾素基因表达的影响 刺激。体外研究表明，虽然早期的醛固酮 生物合成途径增加，Ang II受体含量，mRNA水平 和醛固酮合成酶活性慢性降低。 应激大鼠。这些数据为慢性应激在心脏疾病中的作用提供了证据 高肾素性低醛固酮增多症的发生发展。

The purpose of this project is to study physiological and pathological aspects of the renin-angiotensin system, emphasising its role in circulatory homeostasis and development. During the past year studies have focused on a) the role of type-1 angiotensin II (Ang II) receptors located in parvicellular corticotropin-releasing hormone CRH and CRH/VP cells in the hypothalamic paraventricular nucleus (PVN), and b) the consequenses of chronic stress on the peripheral renin-Ang-aldosterone system. a) The regulation of Ang II receptors in the PVN by glucocorticoids and the role of Ang II regulating the responsiveness of the HPA axis during stress was studied by correlating Ang II receptor expression in the PVN with changes in activity of the HPA axis. Various stress paradigms increased Ang II receptor expression in the parvicellular subdivision of the PVN in similar fashion irrespective of their effect on the activity of the HPA axis. Ang II receptor expresion in parvicellular cells was reduced by adrenalectomy and increased by glucocorticoid administration. The stimulatory effect of stress on Ang II receptor expression in the PVN was prevented by adrenalectomy, indicating that glucocorticoids are necessary for the effect of stress. These data support a role for Ang II in the central mechanisms of adaptation to stress, but indicate that Ang II does not play a role controlling the responsiveness of the HPA axis. b) Repeated physical-psychological stress reduced basal and stimulated aldosterone secretion in spite of elevated basal plasma renin activity. The increases in plasma renin activity were associated with increases in renin mRNA expression in the kidney due to repeated sympathetic stimulation. In vitro studies revealed that while the early aldosterone biosynthetic pathway is increased, Ang II receptor content, mRNA levels and activity of aldosterone synthetase are decreased in chronically stress rats. The data provides evidence for a role of chronic stress in the development of hyperreninemic hypoaldosteronism.