Reversal of hemoglobin-induced vasoconstriction with sustained release of nitric oxide
Reversal of hemoglobin-induced vasoconstriction with sustained release of nitric oxide
复制标题
DOI：
10.1152/ajpheart.00665.2010
复制
发表时间：
2011-01-01
影响因子：
4.8
通讯作者：
Friedman, Joel M.
中科院分区：
文献类型：
--
作者：
Cabrales, Pedro;Han, George;Friedman, Joel M.
Cabrales P，Han G，Nacharaju P，Friedman AJ，Friedman JM.持续释放一氧化氮抑制血红蛋白诱导的血管收缩。美国生理学杂志心脏循环生理学300：H49-H56，2011年。首次发表于2010年11月5日; doi：10.1152/ajpheart.00665.2010.-红细胞游离血红蛋白（Hb）由于一氧化氮（NO）清除而诱导血管收缩，限制了血管平滑肌可用的NO。本研究的中心目的是使用长寿命的循环NO释放纳米颗粒（NO-NP）来逆转聚合牛血红蛋白（PBH）NO清除引起的血管收缩和高血压，以恢复NO的生物利用度。PBH（13 g/dl）的输注量等于动物血容量的10%。通过输注NO-np（10和20 mg/kg体重）提供血管内NO补充。本研究使用仓鼠窗室模型进行，以同时访问全身和微血管血流动力学。灌注PBH使血压升高并引起血管收缩。10和20 mg/kg NO-np可降低PBH引起的血压和血管收缩。此外，与基线相比，较高剂量的NO-np分别降低血压和诱导血管舒张。治疗NO-NP减少PAH引起的血管收缩增加高铁血红蛋白水平和血浆亚硝酸盐和硝酸盐。总之，NO-NP可以抵消全身性高血压，降低PBH输注的血管收缩作用，改善全身和微血管功能。基于观察到的生理特性，NO-np具有作为治疗剂的明确潜力，以在NO产生受损、不足或消耗的情况下补充NO，从而预防血管并发症。
Cabrales P, Han G, Nacharaju P, Friedman AJ, Friedman JM. Reversal of hemoglobin-induced vasoconstriction with sustained release of nitric oxide. Am J Physiol Heart Circ Physiol 300: H49-H56, 2011. First published November 5, 2010; doi:10.1152/ajpheart.00665.2010.-Erythrocyte free hemoglobin (Hb) induces vasoconstriction due to nitric oxide (NO) scavenging, limiting the NO available for vascular smooth muscle. The central objective of this study was to restore NO bioavailability using long-lived circulating NO-releasing nanoparticles (NO-np) to reverse the vasoconstriction and hypertension induced by polymerized bovine Hb (PBH) NO scavenging. PBH (13 g/dl) was infused in a volume equal to 10% of the animal blood volume. Intravascular NO supplementation was provided with an infusion of NO-np (10 and 20 mg/kg body wt). This study was performed using the hamster window chamber model to concurrently access systemic and microvascular hemodynamics. Infusion of PBH increased blood pressure and induced vasoconstriction. Treatment with 10 and 20 mg/kg NO-np reduced the blood pressure and vasoconstriction induced by PBH. Moreover, the higher dose of NO-np decreased blood pressure and induced vasodilation compared with baseline, respectively. Treatment with NO-np to decrease PBH-induced vasoconstriction increased methemoglobin levels and plasma nitrite and nitrate. In conclusion, NO-np counteracted both systemic hypertension and decreased the vasoconstrictor effects of PBH infusion, improving systemic and microvascular function. Based on the observed physiological properties, NO-np has clear potential as a therapeutic agent to replenish NO in situations where NO production is impaired, insufficient, or consumed, thereby preventing vascular complications.