PHYSIOLOGICAL ACTIONS OF THE RENIN-ANGIOTENSIN SYSTEM

这个项目的目的是研究生理和病理 血管紧张素系统的各个方面，强调其在 循环平衡和发育。对新生大鼠的研究显示 醛固酮对血管紧张素II（AII）的反应降低， 大量肾上腺AT 2受体的存在提示发育变化 调节肾上腺肾小球功能的作用。胶原酶 从7日龄大鼠分散的肾上腺肾小球细胞，阻断AT 2 受体对醛固酮产生的刺激没有影响， AII，表明AT2受体不参与类固醇生成。 所有的行动。一个重要的发现是，与成年大鼠相比， AII和ACTH刺激的血浆醛固酮水平以及 醛固酮生物合成途径，醛固酮合成酶， 18小时前给予地塞米松可明显抑制。 用地塞米松预孵育肾上腺细胞2小时， 对基础或刺激的醛固酮产生的影响。的抑制 在体内的影响，并没有阻止促肾上腺皮质激素表明，在新生大鼠 醛固酮分泌受糖皮质激素敏感性的影响， 与ACTH不同。 继续研究禽流感的影响 在人肾系膜细胞中显示融合细胞孵育 AII培养物引起纤维连接蛋白mRNA水平显著增加， 和纤连蛋白合成。AII在表达中的刺激作用 细胞外基质蛋白的表达表明AII参与了 肾小球疾病的发病机制。 AII受体的作用变化， 门静脉高压症患者血管对AII的反应性改变， 在兔门静脉高压症手术模型中进行研究。 AII 血管平滑肌中受体含量显著降低 门静脉高压症肠系膜动、静脉膜 家兔这可能解释了AII引起的升压反应迟钝， 门静脉高压AII受体mRNA的地形图分布为： 使用通过使用引物的PCR获得的cRNA探针在大鼠脑中进行研究 根据大鼠脑组织AT 1受体和cDNA序列，AT1 受体mRNA位于已知含有AT 1受体结合的区域。 此外，AT1受体mRNA在结合区域的表达， 没有显示，如海马和弓状核表明， 低水平受体的存在可以解释报告的 这些地区的生物效应。

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. Studies in neonatal rats showing decreased aldosterone responses to angiotensin II (AII) associated to the presence of abundant adrenal AT2 receptors suggested developmental changes in the regulation of the adrenal glomerulosa function. In collagenase dispersed adrenal glomerulosa cells from 7-day old rats, blockade of AT2 receptors had no effect on the stimulation of aldosterone production by AII, indicating that AT2 receptors are not involved in the steroidogenic actions of AII. An important finding was that in contrast to adult rats, plasma aldosterone levels stimulated by AII and ACTH and the last step of the aldosterone biosynthetic pathway, aldosterone synthetase, were markedly inhibited by administration of dexamethasone 18 hr earlier. Preincubation of isolated adrenal cells with dexamethasone for 2 hr had no effect on basal or stimulated aldosterone production. The inhibitory effect in vivo, was not prevented by ACTH suggesting that in neonatal rats aldosterone secretion is under the influence of a glucocorticoid sensitive factor different from ACTH. Continuation of studies on the effects of AII in human kidney mesangial cells revealed that incubation of confluent cell cultures with AII caused significant increases in fibronectin mRNA level and fibronectin synthesis. The stimulatory effect of AII in the expression of extracellular matrix proteins suggest the involvement of AII in the pathogenesis of glomerular disease. The role of AII receptor changes in the altered vascular responsiveness to AII in portal hypertension was studied in a surgical model of portal hypertension in the rabbit. AII receptor content was significantly decreased in vascular smooth muscle membranes from mesenteric artery and portal vein of portal hypertensive rabbits. This may explain the blunted pressor responses to AII observed in portal hypertension. The topographic distribution of AII receptor mRNA was studied in the rat brain using cRNA probes obtained by PCR using primers based on the sequence of AT1 receptor and cDNA from rat brain. AT1 receptor mRNA was located in ares known to contain AT1 receptor binding. In addition, expression of AT1 receptor mRNA in areas in which binding has not been shown, such as the hippocampus and arcuate nucleus indicate that the presence of low levels of receptors may explain the reported biological effects of AII in these areas.