ADRENOCORTICAL HORMONES IN OBESITY-RELATED HYPERTENSION

肥胖相关高血压中的肾上腺皮质激素

• 批准号: 3356202
• 负责人: ALEXANDER C BROWNIE
• 金额: $ 12.88万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3356202
• 关键词: adrenergic receptor; adrenocorticotropic hormone; aldosterone; androgens; blood pressure; calcium; catecholamines; cholesterol; corticosteroids; corticosterone; cyclic AMP; desoxycorticosterone; disease /disorder model; electron microscopy; endorphins; gel electrophoresis; genetic strain; glucocorticoids; high performance liquid chromatography; hormone receptor; hormone regulation /control mechanism; hypertension; insulin receptor; laboratory rat; melanocyte stimulating hormone; membrane channels; messenger RNA; mineralocorticoids; molecular pathology; myosins; nucleic acid hybridization; nucleic acid probes; nutrition related tag; obesity; phosphorylation; pituitary adrenal axis; proopiomelanocortin; radioimmunoassay; reducing diet; spectrometry; spontaneous hypertensive rat; steroid biosynthesis; steroid hormone biosynthesis; tissue /cell culture; transferase; vascular smooth muscle; vasomotion; weight control

The proposed studies are designed to evaluate the contribution of altered adrenal and pituitary function to the pathogenesis of obesity-related hypertension. The studies will focus on the mechanisms by which increased secretion of hypertensinogenic steroids can occur and lead to hypertension. Adrenal and pituitary function will be examined in vivo and in vitro in fatty Zucker rats, Koletsky obese rats, obese ventromedial nucleus- lesioned rats, congenic spontaneous hypertensive/NIH corpulent rats and appropriate lean controls. In each rat strain, the activity and amount of key enzymes of adrenocortical hormone biosynthesis will be quantitated. The levels of mRNA encoding these enzymes will also be determined using appropriate cDNA probes. Pituitary function will be assessed by measuring and comparing in the various rat strains the levels of pro- opiomelanocortin derived peptides: ACTH, pro-gamma-MSH, alpha-MSH and beta-LPH/endorphin. In parallel and related studies we will examine the interaction of key adrenocortical steroids (glucocorticoids, mineralocorticoids and androgens) with cultured vascular smooth muscle cells isolated from control rats and rats with obesity-related hypertension. The effect(s) of steroid hormones on the content, affinity and specificity of alpha- and beta-adrenergic, insulin and calcium channel receptors will be determined. Receptor activity will be correlated with the kinetics of cAMP formation and/or phosphorylation of myosin light chain-key elements thought to be involved in smooth muscle cell contraction. These studies focus on postulated hormonal changes in obesity- associated hypertension and should provide fundamental information to explain the mechanisms involved.

拟议的研究旨在评估 改变肾上腺和垂体功能的发病机理 与肥胖相关的高血压。 研究将重点放在 通过使高毒素分泌增加的机制 可以发生类固醇并导致高血压。 肾上腺和 垂体功能将在体内和体外检查脂肪 Zucker大鼠，Koletsky肥胖大鼠，肥胖的腹侧核 - 病变的大鼠，先天性自发性高血压/NIH肥胖 大鼠和适当的精益控制。 在每个大鼠菌株中，活性 肾上腺皮质激素的关键酶的数量 生物合成将被定量。 mRNA编码的水平 这些酶也将使用适当的cDNA确定 探针。 垂体功能将通过测量和 比较各种大鼠菌株的促值 Opiomelanocortin衍生的肽：ACTH，Pro-Gamma-MSH， α-MSH和β-LPH/内啡肽。 在并行和相关研究中，我们将研究 关键的肾上腺皮质类固醇（糖皮质激素，盐皮质激素 和雄激素）带有培养的血管平滑肌细胞 与肥胖相关的对照大鼠和大鼠分离 高血压。 类固醇激素对含量的影响， α-和β-肾上腺素能，胰岛素和β-肾上腺素的特异性和特异性 将确定钙通道受体。 受体活性 将与营地形成的动力学和/或 肌球蛋白轻链元素的磷酸化被认为是 参与平滑肌细胞收缩。 这些研究重点是肥胖的荷尔蒙变化 - 相关的高血压，应提供基本 信息以解释所涉及的机制。