Red blood cells prevent inhibition of hypoxic pulmonary vasoconstriction by nitrite in isolated, perfused rat lungs
Red blood cells prevent inhibition of hypoxic pulmonary vasoconstriction by nitrite in isolated, perfused rat lungs
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DOI：
10.1152/ajpheart.00812.2006
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发表时间：
2007-02-01
影响因子：
4.8
通讯作者：
Swenson, Erik R.
中科院分区：
文献类型：
--
作者：
Deem, Steven;Min, Jin-Hye;Swenson, Erik R.
亚硝酸盐还原为一氧化氮（NO）可能是由脱氧血红蛋白的亚硝酸盐还原酶活性增强，并有助于全身缺氧血管舒张。亚硝酸盐对肺循环的影响尚未得到很好的表征。我们探讨了亚硝酸盐对缺氧性肺血管收缩（HPV）的影响以及红细胞（RBC）在亚硝酸盐还原和亚硝酸盐介导的血管舒张中的作用。至于方法，用缓冲液或含RBC的缓冲液灌注离体大鼠肺，并在含或不含亚硝酸盐的情况下进行重复低氧挑战。结果，在缓冲液灌注的肺中，HPV在亚硝酸盐浓度为7 μ M及以上时减少。过量的游离血红蛋白和红细胞阻止了亚硝酸盐对HPV的抑制，这表明血管舒张是由游离NO介导的。轻度酸中毒（pH = 7.2）或黄嘌呤氧化酶活性不会增强亚硝酸盐对HPV的抑制。红细胞在15%，但不是1%的红细胞压积防止抑制HPV的亚硝酸盐（最大亚硝酸盐浓度类似于35 μ M）独立的灌注PO2。亚硝酸盐的降解加速缺氧的存在下，红细胞，但不是在缓冲液灌注。总之，低微摩尔浓度的亚硝酸盐抑制HPV在缓冲液灌注的肺，当红细胞浓度是亚生理。当红细胞浓度接近生理水平时，这种作用消失，尽管在红细胞存在下亚硝酸盐降解增强。这些数据表明，尽管脱氧血红蛋白可以从亚硝酸盐产生NO，但在血液流过肺的动态条件下，不足以使NO逸出RBC以引起肺循环中的血管舒张，并且RBC是NO的净清除剂。
Nitrite reduction to nitric oxide (NO) may be potentiated by a nitrite reductase activity of deoxyHb and contribute to systemic hypoxic vasodilation. The effect of nitrite on the pulmonary circulation has not been well characterized. We explored the effect of nitrite on hypoxic pulmonary vasoconstriction (HPV) and the role of the red blood cell (RBC) in nitrite reduction and nitrite-mediated vasodilation. As to method, isolated rat lungs were perfused with buffer, or buffer with RBCs, and subjected to repeated hypoxic challenges, with or without nitrite. As a result, in buffer-perfused lungs, HPV was reduced at nitrite concentrations of 7 mu M and above. Nitrite inhibition of HPV was prevented by excess free Hb and RBCs, suggesting that vasodilation was mediated by free NO. Nitrite-inhibition of HPV was not potentiated by mild acidosis (pH = 7.2) or xanthine oxidase activity. RBCs at 15% but not 1% hematocrit prevented inhibition of HPV by nitrite ( maximum nitrite concentration of similar to 35 mu M) independent of perfusate PO2. Degradation of nitrite was accelerated by hypoxia in the presence of RBCs but not during buffer perfusion. In conclusion, low micromolar concentrations of nitrite inhibit HPV in buffer-perfused lungs and when RBC concentration is subphysiological. This effect is lost when RBC concentration approaches physiological levels, despite enhanced nitrite degradation in the presence of RBCs. These data suggest that, although deoxyHb may generate NO from nitrite, insufficient NO escapes the RBC to cause vasodilation in the pulmonary circulation under the dynamic conditions of blood flow through the lungs and that RBCs are net scavengers of NO.