VITAMIN D AND SMOOTH MUSCLE FUNCTION

描述：此应用程序的目标是调查 1，25-维生素D3调节血管通畅的机制 肌肉肌球蛋白表达、钙稳态和力量生成。 研究人员此前已经证明，1，25维生素D 增加肌球蛋白调节轻链和肌球蛋白重链蛋白 在主动脉中表达，但在小阻力动脉中不表达。这个 研究人员假设1，25维生素D在区域内发挥作用 对平滑肌的不同作用，也就是 主动脉肌球蛋白原作用与趋钙性作用的区别 在阻力动脉中起作用。这一假设将通过以下方式进行检验： 1.测定1，25维生素D对肌球蛋白亚型的影响 主动脉肌的表达、钙动员和收缩 来自服用1.25维生素D的大鼠，为期三天。2. 确定1，25维生素D是否选择性地调节 肌球蛋白重链的平滑肌特异性亚型。3. 确定1，25维生素D是否增强激动剂诱导的动员 大动脉内的细胞内钙离子。4.确定维生素D是否 通过直接作用于肌丝来增强力量的产生 钙敏感性与钙动员的变化无关。5. 使用阻力动脉，研究人员将确定1，25 维生素D通过增加钙内流来增强钙动员。 6.或确定1，25维生素D是否增加细胞内释放 钙库。7.确定1，25维生素D是否会增加钙含量 通过减少钙外流或减少钙的排出来动员 胞质间隙。调查人员提出，由此产生的 这些研究的信息将具有临床意义，因为1， 25维生素D在血管中升高，并可能对血管起作用 妊娠期高血压和后遗症的病理 更年期妇女服用雌激素补充剂。

DESCRIPTION: The objective of this application is to investigate the mechanisms by which 1,25 vitamin D3 modulates vascular smooth muscle myosin expression, calcium homeostasis and force generation. The investigator has previously demonstrated that 1, 25 vitamin D increases myosin regulatory light chain and myosin heavy chain protein expression in aorta but not in small resistance arteries. The investigator hypothesizes that 1, 25 vitamin D exerts regionally different actions on smooth muscle, that is a differentiating pro-myosin action in the aorta and a calciotropic action in the resistance arteries. This hypothesis will be tested by: 1. Determining the effect of 1, 25 vitamin D on myosin isoform expression, calcium mobilization, and contraction in aortic muscle from rats administered 1, 25 vitamin D for a three day period. 2. Determine if 1, 25 vitamin D selectively modulates expression of the smooth muscle specific isoforms of the myosin heavy chain. 3. Determine if 1, 25 vitamin D enhances agonist induced mobilization of intracellular calcium in the aorta. 4. Determine if vitamin D enhances force generation by a direct effect on myofilament calcium sensitivity unrelated to changes in calcium mobilization. 5. Using resistance arteries, the investigator will determine if 1, 25 vitamin D enhances calcium mobilization by increasing calcium influx. 6. Or determine if 1, 25 vitamin D increases release of intracellular calcium stores. 7. Determine if 1, 25 vitamin D increases calcium mobilization by decreasing calcium efflux or calcium removal from the cytosolic space. The investigator proposes that the resulting information from these studies will be clinically relevant because 1, 25 vitamin D is elevated in, and may contribute to, the vascular pathology in such conditions as gestational hypertension and post- menopausal women on estrogen supplements.