The hypothalamic paraventricular nucleus (PVN) plays crucial roles in central cardiovascular regulation. Increasing evidence in humans and rodents shows that vitamin D intake is important for achieving optimal cardiovascular function. The purpose of this study was to investigate whether calcitriol, an active form of vitamin D, improves autonomic and cardiovascular function in hypertensive rats and whether PVN oxidative stress and inflammation are involved in these beneficial effects. Male spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats were treated with either calcitriol (40 ng/day) or vehicle (0.11 μL/h) through chronic PVN infusion for 4 weeks. Blood pressure and heart rate were recorded continuously by radiotelemetry. PVN tissue, heart and plasma were collected for molecular and histological analysis. Compared to WKY rats, SHR exhibited increased systolic blood pressure, sympathetic drive, and cardiac hypertrophy and remodeling. These were associated with higher mRNA and protein expression levels of high mobility box 1 (HMGB1), receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), proinflammatory cytokines, NADPH oxidase subunit in the PVN. In addition, increased norepinephrine in plasma, elevated reactive oxygen species levels and activation of microglia in the PVN were also observed in SHR. Chronic calcitriol treatment ameliorated these changes but not in WKY rats. Our results demonstrate that chronic infusion of calcitriol in the PVN ameliorates hypertensive responses, sympathoexcitation and retains cardiovascular function in SHR. Reduced inflammation and oxidative stress within the PVN are involved in these calcitriol-induced effects.

下丘脑室旁核（PVN）在中央心血管调节中起关键作用。人体和啮齿动物中越来越多的证据表明，维生素D的摄入对于实现最佳心血管功能很重要。这项研究的目的是研究钙三醇（一种维生素D的活性形式）是否可以改善高血压大鼠的自主神经和心血管功能，以及PVN氧化应激和炎症是否与这些有益作用有关。雄性自发性高血压大鼠（SHR）和血压正常的Wistar Kyoto（WKY）大鼠通过慢性PVN输注钙三醇（40 ng /天）或溶媒（0.11μL/ h）4周。通过无线电遥测法连续记录血压和心率。收集PVN组织，心脏和血浆进行分子和组织学分析。与WKY大鼠相比，SHR表现出收缩压升高，交感神经驱动以及心脏肥大和重塑。这些与高迁移率盒1（HMGB1），晚期糖基化终产物的受体（RAGE），通行费样受体4（TLR4），核因子-κB（NF-κB），促炎性的mRNA和蛋白质表达水平较高相关细胞因子，PVN中的NADPH氧化酶亚基。此外，在SHR中还观察到血浆中去甲肾上腺素升高，活性氧水平升高和PVN中的小胶质细胞活化。慢性骨化三醇治疗改善了这些变化，但在WKY大鼠中却没有改善。我们的结果表明，在PVN中长期输注骨化三醇可改善高血压反应，交感神经兴奋并保留SHR中的心血管功能。