Banday Anees Ahmad, Muhammad Abdul Bari, Fazili Fatima Rizwan, Lokhandwala Mustafa
Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
Hypertension. 2007 Mar;49(3):664-71. doi: 10.1161/01.HYP.0000255233.56410.20. Epub 2007 Jan 2.
High salt intake produces vascular changes that contribute to the development of hypertension in salt-sensitive individuals. Because reactive oxygen species play a role in the pathogenesis of cardiovascular diseases, we investigated whether oxidative stress contributes to salt-sensitive hypertension. Sprague-Dawley rats were divided in different groups and received tap water (vehicle), 30 mmol/L of l-buthionine sulfoximine ([BSO] an oxidant), high salt ([HS] 1% NaCl), and BSO plus HS without and with antioxidant tempol (1 mmol/L) in drinking water for 12 days. Compared with vehicle, BSO treatment caused oxidative stress and mild increase in blood pressure. Thoracic aortic rings from BSO-treated rats exhibited decreased response to endothelium-independent vasorelaxants. In HS-treated rats, the response to vasoactive agents, as well as blood pressure, was unaffected. Concomitant treatment of rats with BSO and HS produced a marked increase in blood pressure and a decreased response to both endothelium-dependent and endothelium-independent vasorelaxants with an increase in EC(50). Incubation of aortic tissue from BSO-treated rats with sodium nitroprusside showed decreased cGMP accumulation, whereas HS rats had decreased basal NO synthase activity. Tempol decreased oxidative stress, normalized blood pressure, and restored NO signaling and responses to vasoactive compounds in BSO and BSO plus HS rats. We conclude that BSO increases oxidative stress and reduces NO signaling, whereas HS reduces NO levels by decreasing the NO synthase activity. These phenomena collectively result in reduced responsiveness to both endothelium -dependent and endothelium- independent vasorelaxants and may contribute to salt-sensitive hypertension.
高盐摄入会引发血管变化，促使盐敏感个体患高血压。由于活性氧在心血管疾病发病机制中起作用，我们研究了氧化应激是否导致盐敏感型高血压。将Sprague-Dawley大鼠分为不同组，分别给予自来水（溶剂对照）、30 mmol/L的L-丁硫氨酸亚砜胺（[BSO]一种氧化剂）、高盐（[HS] 1% NaCl），以及在饮用水中添加和不添加抗氧化剂tempol（1 mmol/L）的BSO加HS，持续12天。与溶剂对照相比，BSO处理导致氧化应激并使血压轻度升高。来自BSO处理大鼠的胸主动脉环对内皮依赖性血管舒张剂的反应降低。在HS处理的大鼠中，对血管活性药物的反应以及血压均未受影响。大鼠同时接受BSO和HS处理后，血压显著升高，对内皮依赖性和内皮依赖性血管舒张剂的反应均降低，且半数有效浓度（EC(50)）增加。用硝普钠孵育BSO处理大鼠的主动脉组织显示环磷酸鸟苷（cGMP）积累减少，而HS大鼠基础一氧化氮合酶（NO synthase）活性降低。Tempol降低了氧化应激，使血压恢复正常，并恢复了BSO和BSO加HS大鼠中NO信号传导以及对血管活性化合物的反应。我们得出结论，BSO增加氧化应激并降低NO信号传导，而HS通过降低NO合酶活性降低NO水平。这些现象共同导致对内皮依赖性和内皮依赖性血管舒张剂的反应性降低，并可能导致盐敏感型高血压。
