RENIN-ANGIOTENSIN SYSTEM AND ALDOSTERONE REGULATION

该项目的目的是分析生理和 病理方面的肾素血管紧张素系统，包括 AII在循环稳态、垂体和性腺中的作用 功能 AII介导醛固酮分泌增加 但是这种肽对肾上腺的影响 取决于球状带对AII的敏感性。 先前在大鼠中的研究表明， 对AII的反应取决于AII的营养效应。 肽和其他调节剂的调节作用， 多巴胺、心钠素（ANF）和生长抑素（SRIF）。 使用多巴胺能拮抗剂甲氧氯普胺（MCP）的研究， 钠负荷下垂体切除大鼠显示， MCP对AII肾上腺效应的影响在 没有垂体。 此外，大量的AII受体， 在改变钠摄入量时， 和MCP给药时，存在于 脑垂体表明一种中间叶因子 参与控制肾上腺对AII的反应。 对AII受体个体发育的研究显示， 受体浓度和分布的变化 发展 除了AII受体显著减少外， 肾上腺包膜和平滑肌中的浓度随年龄增长， 在胎鼠和新生鼠中， 受体广泛分布于肌肉和间质组织 在整个身体。 肾素-AII系统的其他成分是 在胎儿中发现，这表明AII在 发展 受体结合型AII在肾上腺皮质功能中的作用分析 肾小球细胞显示配体的显著内化 在结合激动剂而不是拮抗剂之后。 在 此外，有大量的积累， 激动剂在核表明直接行动的AII在 基因组水平除了公认的膜转导 机制等

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. AII 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 the other regulators such as dopamine, atrial natriuretic factor (ANF) and somatostatin (SRIF). Studies using the dopaminergic antagonist metoclopramide (MCP), in sodium loaded hypo physectomized rats showed that the sensitizing effect of MCP on the adrenal effects of AII is blunted in the absence of the pituitary. In addition, abundant receptors for AII, which undergo regulatory changes during altered sodium intake, AII and MCP administration, are present in the intermediate lobe of the pituitary suggesting that an intermediate lobe factor is involved in the control of the adrenal responsiveness to AII. Studies on the ontogeny of the AII receptor revealed dramatic changes in receptor concentration and distribution during development. In addition to a marked decrease in AII receptor concentration in the adrenal capsule and smooth muscle with age, in fetal and neonatal rat and mouse there are abundant AII receptors widely distributed in muscular and mesenchymal tissue throughout the body. Other components of the renin-AII system were found in the fetus suggesting a unique role of AII during development. Analysis of the role of the receptor bound AII in adrenal glomerulose cells indicated marked internalization of the ligand following binding of the agonist but not the antagonist. In addition, there was significant accumulation of the internalized agonist in the nucleus suggesting direct actions of AII at the genomic level in addition to the recognized membrane transduction mechanisms.