VITAMIN D AND SMOOTH MUSCLE FUNCTION

描述：本申请的目的是调查 1，25维生素D3调节血管平滑肌的机制 肌肉肌球蛋白表达、钙稳态和力产生。 研究人员先前已经证明，125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，而在小阻力动脉中不表达。 的 研究人员假设，1.25维生素D发挥区域性作用， 对平滑肌的不同作用， 区分主动脉中的前肌球蛋白作用和促钙蛋白作用， 在阻力动脉中的作用。该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 表达、钙动员和主动脉肌收缩 从服用了1，25维生素D的大鼠身上，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同种型。3. 确定1，25维生素D是否增强激动剂诱导的动员 细胞内钙离子的浓度4.确定维生素D是否 通过对肌丝的直接作用增强力的产生 钙敏感性与钙动员的变化无关。5. 使用阻力动脉，研究者将确定1、25 维生素D通过增加钙内流增强钙动员。 6.或者确定1，25维生素D是否增加细胞内 钙储存。 7.确定是否1，25维生素D增加钙 通过减少钙流出或从组织中去除钙来动员 胞质间隙研究人员建议， 来自这些研究的信息将是临床相关的， 25维生素D是升高，并可能有助于，血管 病理学在这种情况下，如妊娠高血压和产后 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.