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-血管紧张素系统的研究进展，重点介绍其在 循环动态平衡和发育。血管紧张素Ⅱ受体的表达 包括AT1a和AT1b在内的类型1(AT1)和类型2(AT2)是 在老鼠的发育过程中进行了研究。当AT1a出现在 肾上腺，肾脏，肝脏，卵巢，睾丸，脂肪组织，肺，心脏 而成年小鼠的大脑中，AT1b仅在肾上腺中发现，且很低 睾丸和大脑中的水平。与之形成鲜明对比的是 AT2受体在发育过程中的表达，比例相似 AT1a和AT1b在胎儿和成人的不同组织中均有表达 老鼠。大鼠结合放射自显影和原位研究 杂交显示血管紧张素转换酶AT1和血管紧张素转换酶2的表达相反。 肾脏在出生后的发育过程中。丰富的AT2受体 后肾包块、前移小管和壶腹的表达 未成熟肾脏的输尿管芽，随着时间的推移逐渐减少。 14、肾脏发育完成后消失。相比之下，AT1 出生后2天表达很低，仅限于皮质。 和髓旁边界。血管紧张素转换酶1表达进行性增加 与新发育的肾小球相对应，并从 延髓旁边界至外髓的整个范围。这个 受体亚型表达的时间模式表明 虽然AT2参与细胞增殖和早期分化， AT1受体在肾单位分化中具有双重作用 肾功能。 脑内肾素-AII系统的研究主要集中在AII在脑出血中的作用 下丘脑-垂体-肾上腺轴和加压素的调节 分泌物。原位杂交显示血管紧张素Ⅱ1型受体基因表达 室旁的脑室周围和小细胞心包 下丘脑核(PVN)。放射自显影研究显示所有 结合在与mRNA位置相对应的区域，但除此之外 受体清楚地存在于大细胞的传入纤维中。 PVN的分部。在细胞水平上，原位双重标记 杂交结果显示AT1受体基因定位于促肾上腺皮质激素 释放激素(CRH)神经元，但不存在于加压素和催产素 神经元。此外，中枢应用AII可增加CRH基因的表达。 但不影响PVN中VP基因的表达。数据表明，虽然所有人 通过调节传入信息间接刺激VP的释放 神经支配，AII对CRH神经元有直接的调节作用。

The purpose of this project is to study physiological and pathological aspects of the renin-angiotensin system, with emphasis on its role on circulatory homeostasis and development. The expression of AII receptor subtypes, type-1 (AT1), including AT1a and AT1b, and type-2 (AT2) were studied during development in the mouse. While AT1a was present in the adrenal gland, kidney, liver, ovary, testes, adipose tissue, lung, heart and brain of adult mice, AT1b was found only in the adrenal, and very low levels in testes and brain. In contrast to the marked changes in expression of AT2 receptors during development, similar proportions of AT1a and AT1b in the different tissues were found in fetal and adult mice. Studies in the rat using binding autoradiography and in situ hybridization showed converse changes in the expression of AT1 and AT2 in the kidney during post-natal development. Abundant AT2 receptor expression in the metanephric mass and advancing tubules and ampule of the ureteric bud of the immature kidney, decreased gradually through day- 14, disappearing after completion of nephrogenesis. In contrast, AT1 expression was very low 2 days after birth and was confined to the cortex and juxtamedullary boundary. AT1 expression progressively increased in correspondence to newly developed glomeruli and extended from the juxtamedullary boundary to the whole extent of the outer medulla. The temporal pattern of expression of the receptor subtypes suggests that while AT2 are involved in cell proliferation and early differentiation, AT1 receptors have a dual role in nephron differentiation and later in renal function. Studies on the brain renin-AII system focused on the role of AII in the regulation of the hypothalamic-pituitary-adrenal axis and vasopressin secretion. In situ hybridization studies showed AT1 receptor mRNA in periventricular and parvicellular perikarya of the paraventricular nucleus of the hypothalamus (PVN). Autoradiographic studies showed AII binding in areas corresponding to the mRNA location, but in addition AII receptors were clearly present in afferent fibers to the magnocellular division of the PVN. At the cellular level, double labelling in situ hybridization showed that AT1 receptor mRNA was located in corticotropin releasing hormone (CRH) neurons, but not in vasopressin and oxytocin neurons. In addition, central administration of AII increased CRH mRNA, but not VP mRNA levels in the PVN. The data suggest that while AII stimulates VP release indirectly through modulation of afferent innervation, AII has a direct regulatory effect on the CRH neuron.