CALCIOTROPIC HORMONE ACTION ON ARTERIAL MUSCLE

促钙激素对动脉肌的作用

• 批准号: 2220166
• 负责人: Richard D Bukoski
• 金额: $ 10.89万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-12-12 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2220166
• 关键词: 1,25 dihydroxycholecalciferol; calcitonin; calcitonin gene related peptide; hormone regulation /control mechanism; hypertension; mesenteric artery; muscle contraction; norepinephrine; parathyroid hormones; smooth muscle; tissue /cell culture; vascular resistance

Hypertension is a major health problem which accounts for a significant degree of morbidity and mortality in our population. Both structural and functional changes in the vasculature are believed to contribute to the genesis and maintenance of this disease. Reports of disturbances in Ca2+ homeostasis in several organ systems of both the essential hypertensive human and the spontaneously hypertensive rat (SHR) have served as the basis for the hypothesis that variations in the levels of serum 1,25 VitD, parathyroid hormone (PTH) or calcitonin alter functional properties of vascular muscle. Until recently, however, the vascular effects of these hormones had not been investigated. Our laboratory has found that 1,25 VitD increases 45Ca uptake in cultured aortic myocytes of the SHR and the Wistar Kyoto (WKY) control. 1,25 VitD and PTH were found to differentially modulate norepinephrine (NE)- induced changes in intracellular-free (Ca2+)i in resistance arteries of the SHR and WKY. 1,25 VitD has also been found to modulate growth of vascular myocytes in culture. Our findings have prompted the hypothesis that the calciotropic hormones 1,25 VitD and PTH as well as calcitonin and calcitonin gene-related peptide (CGRP) are modulators of vascular cell contractility, Ca2+ metabolism and growth. A derivative hypothesis is that vascular muscle of the SHR is differentially sensitive to these agents. These hypotheses will be experimentally tested. The effects of 1,25 VitD, PTH, calcitonin and CGRP on contractility and (Ca2+)i of mesenteric resistance arteries will be assessed using a wire myograph and the intracellular dye Fura-2. The effects of these hormones on cellular Ca2+ metabolism will be assessed using both primary and passaged cultures of mesenteric artery myocytes. Indices of Ca2+ metabolism that will be assessed include 45Ca uptake and agonist-induced changes in free (Ca2+)i. Calciotrophic hormone effects on cell growth will be assessed by measuring their effect on both basal and growth factor-induced proliferation. Cellular mechanisms to be examined which might underlie the growth- related actions of these hormones include generation of the inositol polyphosphates and induction of transient changes in free (Ca2+)i and pH. In summary, these experiments will examine metabolism and growth; the results may provide a basis for the development of new perspectives on blood pressure control.

高血压是一个主要的健康问题，它占了 在我们的人口中，发病率和死亡率是相当高的。 血管系统的结构和功能变化都是 据信对这一现象的发生和维持做出了贡献 疾病。几种肌萎缩侧索硬化症的钙稳态紊乱 高血压病患者和老年人的器官系统 自发性高血压大鼠(SHR)已经成为 假设血清1，25-维生素D水平的变化， 甲状旁腺激素或降钙素改变功能特性 血管肌肉。然而，直到最近，血管效应 这些激素中的一种还没有被研究过。我们的实验室有 发现1，25-维生素D增加培养的主动脉摄取45Ca SHR和Wistar京都(WKY)对照组的心肌细胞。1，25维生素D 和甲状旁腺素对去甲肾上腺素(NE)有不同的调节作用。 细胞内游离(Ca~(2+))i诱导的阻力变化 SHR和WKY的动脉。1，25维生素D也被发现 在培养中调节血管肌细胞的生长。 我们的发现引发了一种假设，即趋钙性 激素1，25维生素D和甲状旁腺素以及降钙素和降钙素 基因相关肽是血管细胞的调节剂 收缩、钙代谢和生长。派生假说 自发性高血压大鼠的血管肌肉对 这些特工。这些假设将得到实验验证。这个 1，25-维生素D、甲状旁腺素、降钙素和降钙素基因相关肽对心脏收缩功能的影响 肠系膜阻力动脉的(Ca~(2+))i将用 线式肌电图仪和细胞内染料Fura-2。的影响 这些激素对细胞钙代谢的影响将通过 原代和传代培养肠系膜动脉肌细胞。 将评估的钙代谢指标包括45Ca 摄取和激动剂诱导的游离(Ca~(2+))I.钙营养变化 激素对细胞生长的影响将通过测量它们的 对基础和生长因子诱导的增殖的影响。 需要研究的细胞机制可能是生长的基础- 这些激素的相关作用包括产生 肌醇多聚磷酸盐及其诱导的瞬时游离态变化 (Ca~(2+))i和pH。总而言之，这些实验将检验 新陈代谢和生长；研究结果可能为 血压控制的新视角的发展。