Acute hemolytic vascular inflammatory processes are prevented by @entity842 replacement or a single dose of XXXX .

@entity32 @entity8868 @entity19 @entity1862 @entity12739 @entity3458 @entity842 @entity14451 @entity2142 @entity65762
@entity2142 and consequent release of cell-free hemoglobin (CFHb) impair vascular @entity842 (NO) bioavailability and cause oxidative and inflammatory processes. @entity1862 (HU), a common therapy for @entity3458 ( @entity3458 ), induces fetal Hb production and can act as an NO donor. We evaluated the acute inflammatory effects of intravenous water-induced @entity2142 in C57BL/6 @entity19 and determined the abilities of an NO donor, @entity65762 ( @entity65762 ), and a single dose of HU to modulate this @entity32 . Intravenous water induced acute @entity2142 in C57BL/6 @entity19 , attaining plasma Hb levels comparable to those observed in chimeric @entity3458 @entity19 . This @entity2142 resulted in significant and rapid systemic @entity32 and vascular leukocyte recruitment within 15 minutes, accompanied by NO metabolite generation. Administration of another potent NO scavenger ( @entity12739 ) to C57BL/6 @entity19 induced similar alterations in leukocyte recruitment, whereas @entity8868 -induced @entity32 occurred over a longer time frame. Importantly, the acute inflammatory effects of water-induced @entity2142 were abolished by the simultaneous administration of @entity65762 or HU, without altering CFHb, in an NO pathway-mediated manner. In vitro, HU partially reversed the Hb-mediated induction of endothelial proinflammatory cytokine secretion and adhesion molecule expression. In summary, pathophysiological levels of @entity2142 trigger an immediate inflammatory response, possibly mediated by vascular NO consumption. HU presents beneficial anti-inflammatory effects by inhibiting rapid-onset @entity32 via an NO-dependent mechanism, independently of fetal Hb elevation. Data provide novel insights into mechanisms of @entity32 and further support perspectives for the use of HU as an acute treatment for @entity3458 and other @entity14451 .
