RENIN-ANGIOTENSIN SYSTEM AND ALDOSTERONE REGULATION

这个项目的目的是分析生理学和 肾素血管紧张素系统的病理方面，包括 AII对循环内稳态、垂体和性腺的影响 功能。所有这些都介导了醛固酮分泌的增加。 在限钠期间，但肾上腺多肽的作用 取决于肾小球区对AII的敏感性。 先前在大鼠身上的研究表明，肾上腺 对AII的反应取决于营养效应 肽和其他调节剂的调节作用，如 多巴胺、心钠素和生长抑素 (SRIF)。关于SRIF对肾上腺影响的研究扩展到 灵长类动物。在猴子中发现了SRIF样免疫活性 和人类肾上腺皮质，发现这种多肽 优先抑制血管紧张素Ⅱ刺激的醛固酮生成 分离的猴肾上腺细胞，表明SRIF在 灵长类动物的醛固酮分泌控制。关于中国石油天然气集团公司 重点研究了醛固酮调节剂的作用机制。 ANF对肾上腺和脑垂体的影响。ANF是一个强有力的 刺激cGMP的产生，但环核苷酸没有 抑制类固醇的生成。心钠素抑制的醛固酮 在不影响AII的情况下分泌诱导的胞浆增加 钙或磷脂的周转。花生四烯酸抑制 与ANF特征相似的醛固酮分泌 提示花生四烯酸代谢可能参与了 ANF的作用。ANF刺激的脑垂体细胞内cGMP 不影响基础或刺激垂体腺的生产 荷尔蒙的产生。在性腺中，所有的II受体都存在于 睾丸和颗粒中的间质细胞和黄体细胞 老鼠和灵长类动物的卵巢。在卵巢中激活AII受体 与钙动员和胞浆增加相结合 钙。睾丸和卵巢中AII受体的存在 提示多肽在性腺调节中的作用 功能。

The purpose of this project is to analyze physiological and pathological aspects of the renin angiotensin system, including the effects of AII in circulatory homeostasis, pituitary and gonadal function. All mediates the increase in aldosterone secretion during sodium restriction, but the adrenal effects of the peptide are dependent on the sensitivity of the glomulosa zone to AII. Previous studies in the rat have demonstrated that the adrenal responsiveness to AII depends on the trophic effects of the peptide and the modulatory effect of other regulators such as dopamine, atrial natriuretic factor (ANF) and somatostatin (SRIF). Studies on the adrenal effects of SRIF were extended to the primate. SRIF like immunoactivity was identified in monkey and human adrenal cortex and the peptide was found to preferentially inhibit AII stimulated aldosterone production in isolated monkey adrenal cells, suggesting that SRIF has a role in the control of aldosterone secretion in primates. Studies on the mechanisms of action of aldosterone regulators were focused on the effects ANF in the adrenal and pituitary. ANF was a potent stimulatory cGMP production but the cyclic nucleotide had no inhibitory effect on steroidogenesis. ANF inhibited aldosterone secretion without affecting AII induced increases in cytosolic calcium or phospholipid turnover. Arachidonic acid inhibited aldosterone secretion with characteristics similar to those of ANF suggesting that arachidonic acid metabolism may be involved in the effects of ANF. In pituitary cells ANF stimulated cGMP production without affecting basal or stimulated pituitary hormone production. In the gonads AII receptors are present in Leydig cells in the testes and granulosa and luteal cells to the ovary of rat and primates. In the ovary AII receptor activation by coupled to calcium mobilization with increases in cytosolic calcium. The presence of AII receptors in the testes and ovaries suggest a role for the peptide in the regulation of gonadal function.