Rohlfs R J, Bruner E, Chiu A, Gonzales A, Gonzales M L, Magde D, Magde M D, Vandegriff K D, Winslow R M
Department of Medicine, School of Medicine, University of California, San Diego, Veterans Affairs Medical Center, San Diego, California 92161, USA.
J Biol Chem. 1998 May 15;273(20):12128-34. doi: 10.1074/jbc.273.20.12128.
Changes in mean arterial pressure were monitored in rats following 50% isovolemic exchange transfusion with solutions of chemically modified hemoglobins. Blood pressure responses fall into three categories: 1) an immediate and sustained increase, 2) an immediate yet transient increase, or 3) no significant change either during or subsequent to exchange transfusion. The reactivities of these hemoglobins with nitric monoxide (.NO) were measured to test the hypothesis that different blood pressure responses to these solutions result from differences in .NO scavenging reactions. All hemoglobins studied exhibited a value of 30 microM-1 s-1 for both .NO bimolecular association rate constants and the rate constants for .NO-induced oxidation in vitro. Only the .NO dissociation rate constants and, thus, the equilibrium dissociation constants varied. Values of equilibrium dissociation constants ranged from 2 to 14 pM and varied inversely with vasopressor response. Hemoglobin solutions that exhibited either transient or no significant increase in blood pressure showed tighter .NO binding affinities than hemoglobin solutions that exhibited sustained increases. These results suggest that blood pressure increases observed upon exchange transfusion with cell-free hemoglobin solutions can not be the result of .NO scavenging reactions at the heme, but rather must be due to alternative physiologic mechanisms.
用化学修饰血红蛋白溶液对大鼠进行50%等容交换输血后,监测其平均动脉压的变化。血压反应分为三类:1)立即且持续升高;2)立即但短暂升高;3)在交换输血期间或之后无显著变化。测量这些血红蛋白与一氧化氮(.NO)的反应性,以检验以下假设:对这些溶液的不同血压反应是由于.NO清除反应的差异所致。所有研究的血红蛋白在体外.NO双分子缔合速率常数和.NO诱导氧化的速率常数均显示为30 microM-1 s-1。只有.NO解离速率常数以及平衡解离常数有所不同。平衡解离常数的值在2至14 pM之间,且与血管升压反应呈反比。与血压持续升高的血红蛋白溶液相比,血压短暂升高或无显著升高的血红蛋白溶液表现出更强的.NO结合亲和力。这些结果表明,用无细胞血红蛋白溶液进行交换输血时观察到的血压升高并非血红素处.NO清除反应的结果,而必定是由于其他生理机制所致。