Kilbourn R G, Joly G, Cashon B, DeAngelo J, Bonaventura J
Department of Genitourinary Oncology, University of Texas M. D. Anderson Cancer Center, Houston.
Biochem Biophys Res Commun. 1994 Feb 28;199(1):155-62. doi: 10.1006/bbrc.1994.1208.
Hemoglobin (Hbg) and lysates of red blood cells act as vasoconstrictors in isolated vessels by a mechanism that may involve nitric oxide (NO.) scavenging. To determine if such a mechanism indeed occurs, we investigated the effects of cell-free Hgb, modified Hgp (met Hgb and cyan met Hgb), and red blood cells on the formation of NO. induced by endotoxin in rat aorta. Incubation of rat aortic rings with endotoxin induced a delayed and prolonged release of NO. that resulted in a decrease in the contractile response to phenylephrine. Hgb significantly potentiated contractions to phenylephrine in control rings and also reversed the hyporeactivity to this alpha 1-agonist in endotoxin-treated rings with and without endothelium. Lysed red blood cells but not whole red blood cells shifted the concentration-contraction response curves to phenylephrine significantly to the right in endotoxin-treated preparations. Neither picket-fence porphyrin-albumin (PFP-albumin) or metheme-albumin affected the contractile response to phenylephrine. Oxidation of Hgb to met Hgb did not alter the contractions to an alpha 1-agonist in endotoxin-treated rings. In contrast, the formation of cyan met Hgb abolished the action of Hgb on the vascular reactivity of endotoxin-treated preparations. Together, these results demonstrate that free Hgb can scavenge NO. produced in endotoxin-treated vascular tissue and that the ability to bind NO. requires a cell-free form of Hgb with an intact heme center capable of undergoing redox reactions.
血红蛋白（Hbg）和红细胞裂解物在离体血管中可作为血管收缩剂，其作用机制可能涉及一氧化氮（NO）清除。为确定是否确实存在这样一种机制，我们研究了无细胞血红蛋白、修饰的血红蛋白（高铁血红蛋白和氰化高铁血红蛋白）以及红细胞对内毒素诱导的大鼠主动脉中NO生成的影响。用内毒素孵育大鼠主动脉环可诱导NO的延迟和持续释放，这导致对去氧肾上腺素的收缩反应减弱。在对照环中，血红蛋白显著增强了对去氧肾上腺素的收缩作用，并且在有或无内皮的内毒素处理环中，也逆转了对这种α1激动剂的反应性降低。在经内毒素处理的制剂中，裂解的红细胞而非完整红细胞使去氧肾上腺素的浓度 - 收缩反应曲线显著右移。栅栏卟啉 - 白蛋白（PFP - 白蛋白）或高铁血红素 - 白蛋白均未影响对去氧肾上腺素的收缩反应。在经内毒素处理的环中，血红蛋白氧化为高铁血红蛋白并未改变对α1激动剂的收缩作用。相反，氰化高铁血红蛋白的形成消除了血红蛋白对内毒素处理制剂血管反应性的作用。总之，这些结果表明游离血红蛋白可清除内毒素处理的血管组织中产生的NO，并且结合NO的能力需要无细胞形式的血红蛋白，其具有完整的能够进行氧化还原反应的血红素中心。
