Parathyroid Hormone & Vitamin D Effects on Salt Sensitivity and Vascular Function

描述（由申请人提供）：维生素D缺乏症在非洲裔美国人中比白人更常见。在非裔美国人中，甲状旁腺激素（PTH）升高的患病率也很高，这通常是维生素D水平降低和/或钙摄入量低的结果。肥胖，不成比例地影响非洲裔美国人（特别是妇女），也与维生素D缺乏症和PTH升高的过度流行有关。然而，通过慢性PTH升高维持血清钙浓度在脉管系统和心肌内具有已知的有害生理作用，例如血管收缩、成纤维细胞活化、胰岛素抵抗、血脂异常、脂肪沉积和内皮一氧化氮的下调-所有这些都可能导致血压（BP）升高和血管和压力敏感性靶器官损伤、体重增加、血脂异常、和葡萄糖耐受不良我们提出了一项在NIH资助的ONOSS研究中招募的约65名健康，血压正常的非裔美国人中进行的研究，以检查6周膳食钠补充剂前后的以下情况：目标#1：测定血压（BP）（袖带和非卧床24小时），动脉僵硬度（AS），外周血管阻力（PVR）和一氧化氮（NO）产生及其与基线时25-OH维生素D（25-OH D）和PTH循环水平的关系;目标#2：确定基线25-OH D和PTH水平与饮食盐负荷后BP、AS和PVR的后续变化的关系;目标#3：确定NO代谢物的变化和血小板中刺激的NO产生与饮食盐负荷后BP、AS和PVR的变化的关系;目标#4：确定基线25-OH D和PTH水平与氧化应激循环标志物基线水平的相关性（总异前列腺素、核因子κ β）和自由基（硝基酪氨酸，二酪氨酸，氯酪氨酸），并反过来将氧化应激的循环标志物与BP，AS，PVR，尿NO代谢物，和血小板在饮食盐负荷后NO的产生相关性：维生素D缺乏和继发性PTH增加是常见的，特别是在肥胖者和非裔美国人中。它们都具有血管和生理效应，导致非裔美国人中血压升高、血管和压力相关靶器官损伤、内皮功能障碍和盐敏感性的过度流行。重要的是要了解维生素D缺乏和PTH长期升高对可能导致常见心血管并发症的异常生理的作用，因为维生素D补充剂价格实惠，相对无毒，并且可以口服制剂。

DESCRIPTION (provided by applicant): Vitamin D deficiency is much more common in African Americans than whites. The prevalence of elevated parathyroid hormone (PTH), typically a consequence of depressed vitamin D levels and/or low calcium intake, is also high in African Americans. Obesity, which disproportionately affects African Americans (especially women), has also been linked to an excessive prevalence of vitamin D deficiency and elevated PTH. However, maintenance of serum calcium concentrations by chronic PTH elevations has known deleterious physiological effects within the vasculature and myocardium such as vasoconstriction, activation of fibroblasts, insulin resistance, dyslipidemia, fat deposition and down regulation of endothelial nitric oxide - all of which plausibly contribute to elevated blood pressure (BP)and vascular and pressure- sensitive target organ injury, weight gain, dyslipidemia, and glucose intolerance. We propose a study in ~ 65 healthy, normotensive African Americans enrolled in the NIH-funded ONOSS study to examine the following before and after a 6 week period of dietary sodium supplementation: Aim #1: determine blood pressure (BP)(cuff and ambulatory 24 hour), arterial stiffness (AS), peripheral vascular resistance(PVR) and nitric oxide (NO)production and their relation to circulating levels of 25-OH vitamin D (25-OH D) and PTH at baseline; Aim #2: determine the relationship of baseline 25-OH D and PTH levels with subsequent changes in BP, AS, and PVR after dietary salt loading; Aim #3:Determine the relationship of the change in NO metabolites and stimulated NO production in platelets to changes in BP, AS and PVR after dietary salt loading; Aim #4: Determine the association of baseline 25-OH D and PTH levels with baseline levels of circulating markers of oxidative stress (total isoprostanes, nuclear factor kappa beta) and free radicals (nitrotyrosine, dityrosine, chlorotyrosine), and in turn, link circulating markers of oxidative stress to changes in BP, AS, PVR, urinary NO metabolites, and platelet production of NO after dietary salt loading Relevance: Vitamin D deficiency and secondary increase in PTH are common, particularly amongst obese persons and African Americans. They both have vascular and physiological effects that lead to the excessive prevalence of elevated BP, vascular and pressure-related target-organ injury, endothelial dysfunction, and salt sensitivity in African Americans. It is important to understand the role of vitamin D deficiency and prolonged elevation of PTH to the abnormal physiology that likely contributes to common cardiovascular complication since vitamin D supplementation is affordable, relatively non-toxic, and is available in oral formulations.