Banday Anees Ahmad, Lokhandwala Mustafa F
Heart and Kidney Institute, College of Pharmacy, Univ. of Houston, 4800 Calhoun Road, Houston, TX 77204, USA.
Am J Physiol Renal Physiol. 2009 Aug;297(2):F397-402. doi: 10.1152/ajprenal.90729.2008. Epub 2009 May 27.
Renal dopamine and nitric oxide contribute to natriuresis during high-salt intake which maintains sodium and blood pressure homeostasis. We wanted to determine whether concurrent inhibition of these natriuretic factors increases blood pressure during high-sodium intake. Male Sprague-Dawley rats were divided into the following groups: 1) vehicle (V)-tap water, 2) NaCl-1% NaCl drinking water, 3) 30 mM l-buthionine sulfoximine (BSO), an oxidant, 4) BSO plus NaCl, and 5) BSO plus NaCl with 1 mM tempol (antioxidant). Compared with V, NaCl intake for 10 days doubled sodium intake and increased urinary dopamine level but reduced urinary nitric oxide content. NaCl intake also reduced basal renal proximal tubular Na-K-ATPase activity with no effect on blood pressure. However, NaCl intake in BSO-treated rats failed to reduce basal Na-K-ATPase activity despite higher urinary dopamine levels. Also, dopamine failed to inhibit proximal tubular Na-K-ATPase activity and these rats exhibited reduced urinary nitric oxide levels and high blood pressure. Tempol supplementation in NaCl plus BSO-treated rats reduced blood pressure. BSO treatment alone did not affect the urinary nitric oxide and dopamine levels or blood pressure. However, dopamine failed to inhibit proximal tubular Na-K-ATPase activity in BSO-treated rats. BSO treatment also increased basal protein kinase C activity, D1 receptor serine phosphorylation, and oxidative markers like malondialdehyde and 8-isoprostane. We suggest that NaCl-mediated reduction in nitric oxide does not increase blood pressure due to activation of D1 receptor signaling. Conversely, oxidative stress-provoked inhibition of D1 receptor signaling fails to elevate blood pressure due to presence of normal nitric oxide. However, simultaneously decreasing nitric oxide levels with NaCl and inhibiting D1 receptor signaling with BSO elevated blood pressure.
肾脏多巴胺和一氧化氮在高盐摄入期间有助于利钠，从而维持钠和血压的稳态。我们想确定同时抑制这些利钠因子是否会在高钠摄入期间升高血压。雄性Sprague-Dawley大鼠被分为以下几组：1）溶剂对照组（V）——饮用自来水；2）NaCl组——饮用1% NaCl饮用水；3）30 mM L-丁硫氨酸亚砜胺（BSO）组，一种氧化剂；4）BSO加NaCl组；5）BSO加NaCl并补充1 mM Tempol（抗氧化剂）组。与V组相比，摄入10天NaCl使钠摄入量增加了一倍，尿多巴胺水平升高，但尿一氧化氮含量降低。NaCl摄入还降低了基础肾近端小管钠钾ATP酶活性，对血压无影响。然而，在BSO处理的大鼠中，尽管尿多巴胺水平较高，但NaCl摄入未能降低基础钠钾ATP酶活性。此外，多巴胺未能抑制近端小管钠钾ATP酶活性，这些大鼠的尿一氧化氮水平降低且血压升高。在NaCl加BSO处理的大鼠中补充Tempol可降低血压。单独使用BSO处理不影响尿一氧化氮和多巴胺水平或血压。然而，在BSO处理的大鼠中，多巴胺未能抑制近端小管钠钾ATP酶活性。BSO处理还增加了基础蛋白激酶C活性、D1受体丝氨酸磷酸化以及丙二醛和8-异前列腺素等氧化标志物。我们认为，NaCl介导的一氧化氮减少不会因D1受体信号激活而升高血压。相反，由于正常一氧化氮的存在，氧化应激引发的D1受体信号抑制不会升高血压。然而，同时用NaCl降低一氧化氮水平并用BSO抑制D1受体信号会升高血压。
