SYMPATHETIC NERVOUS SYSTEM AND NITRIC OXIDE IN SALT INDUCED HYPERTENSION

盐敏感性/膳食钠与糖尿病发病的关系 高血压被广泛接受。然而，尽管有广泛的 这方面已经做过的研究，具体机制(S) 与盐诱导的高血压有关的因素仍不清楚。长期目标 这项研究项目的目的是检验食盐的假设 通过改变血管反应性来增加血压，部分通过 增强交感神经活性和抑制一氧化氮 活动/功能。具体目的是：1)检视机制(S) 参与盐性高血压的发病机制，强调 男性和女性的心血管、血流动力学和血管反应性， 清醒的达尔大鼠对盐敏感和耐盐。2) 阐明信号转导途径和离子通道参与 一氧化氮、环磷酸鸟苷、神经递质与盐性高血压的关系 在离体主动脉内释放和Ca/2+。血压和心率 将通过尾部体积描记仪间接测量以及直接在 清醒的老鼠。心输出量和每搏输出量将使用 计算心尖周长II和总外周阻力。血管 对硝普钠、苯肾上腺素和去甲肾上腺素的反应性 肾上腺素能受体和交感神经刺激的影响以及 钙/2+通道阻滞剂的作用将在意识和 被打了洞的老鼠。血液流向离散的血管床(主动脉、肠系膜和 肾脏)将使用跨音速流量计进行测定。血液样本将 从植入股动脉的动脉导管收集。 血浆儿茶酚胺和cGMP水平将用高 高效液相色谱-电化学检测和 放射免疫分析。CAMP和cGMP水平及 大鼠离体主动脉细胞内钙离子也将被测量 内皮细胞。从这些研究中得出的数据将提供新的 与性别差异以及心血管和细胞疾病相关的见解 盐诱导高血压的作用机制(S)。

The link between salt-sensitivity/dietary sodium and the development of high blood pressure is widely accepted. However, in spite of the extensive research that has been done in this area, the specific mechanism(s) involved in salt-induced hypertension remain unclear. The long-term goal of this research project is to examine the hypothesis that dietary salt increased blood pressure by modifying vascular reactivity, in part, via enhancement of sympathetic activity and suppression of nitric oxide activity/function. The specific aims are: 1) Examine the mechanism(s) involved in the pathogenesis of salt-induced hypertension with emphasis on cardiovascular, hemodynamics and vascular reactivity, in male and female, conscious and pithed Dahl salt-sensitive and salt-resistant rats. 2) Elucidate the signal transduction pathways and ion channels involved in salt-induced hypertension by nitric oxide, cyclic GMP, neurotransmitter release and Ca/2+ in the isolated aorta. Blood pressure and heart rate will be measured indirectly by tail plethysmography as well as directly in conscious rats. Cardiac output and stroke volume will be measured using a Cardiomax II and total peripheral resistance calculated. Vascular reactivity to sodium nitroprusside, phenylephrine and norepinephrine as influence by -adrenoceptors and sympathetic stimulation as well as the effect of Ca/2+ channel blocker will be evaluated in both conscious and pithed rats. Blood flow to discrete vascular beds (aortic, mesenteric and renal) will be determined using a Transonic flow-meter. Blood samples will be collected from arterial catheters implanted in the femoral arteries. Plasma levels of catecholamine and cGMP will be assayed by high performance liquid chromatography with electrochemical detection and radio-immunoassay, respectively. Cyclic AMP and cGMP levels and intracellular Ca/2+ will also be measure din isolated rat aorta endothelial cells. Data derived from these studies will provide new insights related to gender differences and cardiovascular and cellular mechanism(s) involved in salt-induced hypertension.