CALCIOTROPIC HORMONE ACTION ON ARTERIAL MUSCLE

高血压是一个主要的健康问题， 我国人口发病率和死亡率很高。 血管系统的结构和功能变化都是 据信有助于这一现象的发生和维持 疾病 报道了几种细胞中Ca 2+稳态的紊乱 原发性高血压患者和 自发性高血压大鼠（SHR）已作为基础， 假设血清1，25 VitD水平的变化， 甲状旁腺激素（PTH）或降钙素改变功能特性 血管肌肉。 然而，直到最近， 这些激素还没有被研究过。 本实验室 发现1，25 VitD增加培养的主动脉45 Ca摄取 自发性高血压大鼠和京都大白鼠（WKY）对照组的心肌细胞。 1.25维生素D 和甲状旁腺素被发现差异调节去甲肾上腺素（NE）- 诱导细胞内游离钙离子浓度的变化 SHR和WKY的动脉。 1，25 VitD也被发现 调节培养物中血管肌细胞的生长。 我们的发现提示了这样一种假设， 激素1，25 VitD和PTH以及降钙素和降钙素 基因相关肽（CGRP）是血管细胞 收缩力、Ca 2+代谢和生长。 衍生假设 SHR的血管肌肉对 这些代理人。 这些假设将通过实验进行检验。 的 1，25 VitD、PTH、降钙素和CGRP对收缩力的影响， (Ca2+）肠系膜阻力动脉的i将使用 钢丝肌描记器和细胞内染料Fura-2 的影响 这些激素对细胞Ca 2+代谢的影响将使用 肠系膜动脉肌细胞的原代和传代培养物。 将评估的Ca 2+代谢指标包括45 Ca 摄取和激动剂诱导的游离（Ca 2+）变化i. 钙营养的 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。 细胞机制有待研究，这可能是生长的基础- 这些激素的相关作用包括产生 肌醇多磷酸和诱导游离 (Ca2总之，这些实验将检查 代谢和生长;结果可能提供了一个基础， 发展血压控制的新观点。

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.