Barton Cyril H, Ni Zhenmin, Vaziri Nosratola D
Division of Nephrology and Hypertension, University of California, Irvine, Orange, California 92868, USA.
Am J Hypertens. 2003 Dec;16(12):1043-8. doi: 10.1016/j.amjhyper.2003.07.021.
Chronic exposure to hypobaric hypoxia has been shown to increase arterial pressure in genetically normal rats. The associated increase in blood pressure is unrelated to the hypoxia-induced erythrocytosis and persists indefinitely after restoration of normoxia. It is accompanied by a marked reduction in urinary excretion of nitric oxide metabolites (NOx) and is ameliorated by L-arginine supplementation. In view of the latter observations, we hypothesized that hypoxia-induced hypertension may be associated with downregulation of NO synthase (NOS).
Male Sprague Dawley rats were randomized to the hypoxic and control groups. Rats assigned to the hypoxic group were placed in chambers with air pressure maintained at 390 mm Hg. Animals assigned to the control group were kept in the chamber at 760 mm Hg air pressure. Animals were kept in their respective conditions for up to 21 days. Group of animals were tested at days 2, 3, 7, and 21.
The hypoxic group exhibited a steady increase in arterial pressure beginning at day 3. This was accompanied by a transient increase followed by a significant decline in kidney NOS-I, NOS-II, and NOS-III abundance. A similar biphasic change was observed with NOS-II and NOS-III in the cardiac and vascular tissues. The changes in NOS abundance in the given tissues were associated with parallel changes in nitrotyrosine abundance, which reflects local NO production. The latter finding provides functional evidence for the changes observed in NOS abundance.
Chronic hypoxia-induced hypertension in rats is associated with marked downregulation of NOS isotypes, which can, in part, account for the previously reported L-arginine-responsive hypertension in this model.
研究表明，长期暴露于低压低氧环境会使基因正常的大鼠动脉血压升高。血压升高与低氧诱导的红细胞增多症无关，且在恢复常氧后会持续存在。同时，尿中一氧化氮代谢产物（NOx）排泄显著减少，补充L-精氨酸可改善这种情况。基于这些观察结果，我们推测低氧诱导的高血压可能与一氧化氮合酶（NOS）下调有关。
将雄性Sprague Dawley大鼠随机分为低氧组和对照组。低氧组大鼠置于气压维持在390 mmHg的舱室中。对照组大鼠置于气压为760 mmHg的舱室中。动物在各自条件下饲养长达21天。分别在第2、3、7和21天对动物进行检测。
低氧组从第3天开始动脉血压稳步升高。与此同时，肾脏中NOS-I、NOS-II和NOS-III的丰度先短暂升高，随后显著下降。心脏和血管组织中的NOS-II和NOS-III也出现类似的双相变化。特定组织中NOS丰度的变化与硝基酪氨酸丰度的平行变化相关，硝基酪氨酸丰度反映局部NO生成。后一发现为NOS丰度变化提供了功能证据。
大鼠慢性低氧诱导的高血压与NOS亚型的显著下调有关，这在一定程度上可以解释该模型中先前报道的L-精氨酸反应性高血压。
