Effects of S-nitrosation of hemoglobin on hypoxic pulmonary vasoconstriction and nitric oxide flux

Free hemoglobin (Hb) augments hypoxic pulmonary vasoconstriction (HPV), ost ensibly by scavenging nitric oxide (NO). However, recent evidence suggests that Hb that is S-nitrosated may act as an NO donor and vasodilator. We stu died the effects of oxyHb, Hb that is chemically modified to prevent heme b inding or oxidation of NO (cyanometHb), and Hb that is S-nitrosated (SNO-Hb and SNO-cyanometHb) on HPV, expired NO (eNO), and perfusate S-nitrosothiol (SNO) concentration in isolated, perfused rabbit lungs. Perfusate containi ng either 4 muM oxyHb or SNO-Hb increased normoxic pulmonary artery pressur e (Ppa), augmented HPV dramatically, and resulted in an 80% fall in eNO in comparison to perfusion with buffer, whereas 4 muM cyanometHb or SNO-cynano metHb had no effect on these variables. Excess glutathione (GSH) added to p erfusate containing SNO-Hb resulted in a 20 to 40% fall in the perfusate SN O concentration, with a concomitant increase in metHb content, without affe cting Ppa, HPV, or eNO. In conclusion, free Hb augments HPV by scavenging N O, an effect that is not prevented by S-nitrosation. NO released from SNO-H b in the presence of GSH does not produce measurable vascular effects in th e lung or changes in eNO because of immediate oxidation and metHb formation .