Li Hui, Teng Xu, Yang Rui, Guo Qi, Xue Hongmei, Xiao Lin, Duan Xiaocui, Tian Danyang, Feng Xiaohong, Wu Yuming
Department of Physiology, Institute of Basic Medicine, Hebei Medical UniversityShijiazhuang, China.
Hebei Key Lab of Laboratory Animal Science, Hebei Medical UniversityShijiazhuang, China.
Front Pharmacol. 2017 Sep 12;8:629. doi: 10.3389/fphar.2017.00629. eCollection 2017.
Arterial baroreflex is a general mechanism maintaining cardiovascular homeostasis; its sensitivity is reduced in vascular calcification (VC). Hydrogen sulfide (HS) treatment facilitates baroreflexive sensitivity in normal and hypertensive rats. Here, we aimed to detect the effect of HS on baroreflexive sensitivity in rats with VC. The rat VC model was induced by vitamin D plus nicotine for 4 weeks. The sensitivity of baroreflex was detected by perfusing the isolated carotid sinus. VC was assessed by hematoxylin and eosin (H&E) staining, Ca content and alkaline phosphatase (ALP) activity. Protein levels were detected by western blot analysis. Vitamin D plus nicotine induced structural disorder and elevated Ca content in the aortic and carotid arterial wall and increased plasma ALP activity. In the calcified aorta and carotid artery, protein levels of contractile phenotype markers of vascular smooth muscle cells (VSMCs) were downregulated and that of osteoblast-like phenotype markers and endoplasmic reticulum stress (ERS) markers were upregulated. NaHS treatment ameliorated the histologic disorder and Ca content in the calcified aorta and carotid artery, inhibited the elevated plasma ALP activity, and prevented the transformation of the VSMC phenotype and activation of ERS in rats with VC. Chronic NaHS treatment prevented the impairment of the baroreflex sensitivity and acute NaHS treatment dose-dependently improved the sensitivity in rats with VC. Our results suggested that HS could directly facilitate the impairment of baroreflex in rats with VC and ameliorate VC, which might provide new target and strategy for regulation of the baroreflex and therapy of VC.
动脉压力反射是维持心血管稳态的一种普遍机制；其敏感性在血管钙化（VC）时降低。硫化氢（HS）治疗可促进正常和高血压大鼠的压力反射敏感性。在此，我们旨在检测HS对VC大鼠压力反射敏感性的影响。通过维生素D加尼古丁诱导大鼠VC模型4周。通过灌注离体颈动脉窦检测压力反射的敏感性。通过苏木精-伊红（H&E）染色、钙含量和碱性磷酸酶（ALP）活性评估VC。通过蛋白质印迹分析检测蛋白质水平。维生素D加尼古丁导致主动脉和颈动脉壁结构紊乱、钙含量升高以及血浆ALP活性增加。在钙化的主动脉和颈动脉中，血管平滑肌细胞（VSMC）收缩表型标志物的蛋白质水平下调，而成骨细胞样表型标志物和内质网应激（ERS）标志物的蛋白质水平上调。NaHS治疗改善了钙化主动脉和颈动脉的组织学紊乱和钙含量，抑制了血浆ALP活性升高，并防止了VC大鼠VSMC表型转化和ERS激活。慢性NaHS治疗可防止压力反射敏感性受损，急性NaHS治疗剂量依赖性地改善了VC大鼠的敏感性。我们的结果表明，HS可直接减轻VC大鼠的压力反射损害并改善VC，这可能为调节压力反射和治疗VC提供新的靶点和策略。
