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: 3356204
• 负责人: ALEXANDER C BROWNIE
• 金额: $ 12.65万
• 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/3356204
• 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的贡献 肾上腺和垂体功能的改变对发病机制的影响 肥胖相关的高血压。 研究将集中于 增加致高血压素分泌的机制 类固醇可能会发生并导致高血压。 肾上腺和 垂体功能将在体内和体外在脂肪中进行检查 Zucker大鼠、Koletsky肥胖大鼠、肥胖腹内侧核- 病变大鼠，同源自发性高血压/NIH 肥胖 大鼠和适当的瘦对照。 在每个大鼠品系中，活性 肾上腺皮质激素关键酶的含量和含量 生物合成将被定量。 mRNA编码水平 这些酶也将使用适当的 cDNA 来确定 探针。 垂体功能将通过测量和 比较不同大鼠品系的亲水平 阿片黑皮质素衍生肽：ACTH、pro-gamma-MSH、 α-MSH 和 β-LPH/内啡肽。 在平行和相关的研究中，我们将研究以下相互作用： 关键肾上腺皮质类固醇（糖皮质激素、盐皮质激素 和雄激素）与培养的血管平滑肌细胞 从对照大鼠和肥胖相关大鼠中分离 高血压。 类固醇激素对其含量的影响， α- 和 β- 肾上腺素、胰岛素和 钙通道受体将被确定。 受体活性 将与 cAMP 形成的动力学相关和/或 肌球蛋白轻链的磷酸化——被认为是关键元件 参与平滑肌细胞的收缩。 这些研究重点关注假设的肥胖荷尔蒙变化—— 相关高血压，应提供基本的 解释所涉及机制的信息。