Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, 14049-900 Ribeirao Preto, SP, Brazil.
Free Radic Biol Med. 2011 Jul 1;51(1):144-52. doi: 10.1016/j.freeradbiomed.2011.04.005. Epub 2011 Apr 13.
Dietary nitrite and nitrate are important sources of nitric oxide (NO). However, the use of nitrite as an antihypertensive drug may be limited by increased oxidative stress associated with hypertension. We evaluated the antihypertensive effects of sodium nitrite given in drinking water for 4 weeks in two-kidney one-clip (2K1C) hypertensive rats and the effects induced by nitrite on NO bioavailability and oxidative stress. We found that, even under the increased oxidative stress conditions present in 2K1C hypertension, nitrite reduced systolic blood pressure in a dose-dependent manner. Whereas treatment with nitrite did not significantly change plasma nitrite concentrations in 2K1C rats, it increased plasma nitrate levels significantly. Surprisingly, nitrite treatment exerted antioxidant effects in both hypertensive and sham-normotensive control rats. A series of in vitro experiments was carried out to show that the antioxidant effects induced by nitrite do not involve direct antioxidant effects or xanthine oxidase activity inhibition. Conversely, nitrite decreased vascular NADPH oxidase activity. Taken together, our results show for the first time that nitrite has antihypertensive effects in 2K1C hypertensive rats, which may be due to its antioxidant properties resulting from vascular NADPH oxidase activity inhibition.
饮食中的亚硝酸盐和硝酸盐是一氧化氮（NO）的重要来源。然而，亚硝酸盐作为一种降压药物的使用可能会受到与高血压相关的氧化应激增加的限制。我们评估了在两周肾一夹（2K1C）高血压大鼠的饮水中给予亚硝酸盐 4 周的降压作用，以及亚硝酸盐对 NO 生物利用度和氧化应激的影响。我们发现，即使在 2K1C 高血压中存在增加的氧化应激条件下，亚硝酸盐也以剂量依赖的方式降低收缩压。虽然亚硝酸盐治疗并没有显著改变 2K1C 大鼠的血浆亚硝酸盐浓度，但它显著增加了血浆硝酸盐水平。令人惊讶的是，亚硝酸盐治疗在高血压和假正常血压对照大鼠中均发挥了抗氧化作用。进行了一系列体外实验以表明，亚硝酸盐诱导的抗氧化作用不涉及直接的抗氧化作用或黄嘌呤氧化酶活性抑制。相反，亚硝酸盐降低了血管 NADPH 氧化酶活性。总之，我们的结果首次表明，亚硝酸盐在 2K1C 高血压大鼠中具有降压作用，这可能是由于其血管 NADPH 氧化酶活性抑制导致的抗氧化特性。
