Abstract
Acellular hemoglobin (Hb) derivates developed as oxygen carriers are known to cause hypertensive reactions due to their nitric oxide (NO) scavenging action. To modulate this undesired activity, we have developed a new Hb derivative, s-nitrosylated polyethylene glycol (PEG)-modified hemoglobin (SNO-PEG-Hb), which can deliver oxygen and NO. After human Hb was modified with PEG to increase its molecular weight, the free sulfhydryl groups of Hb were s-nitrosylated with s-nitrosoglutathione. Administration of unmodified Hb into anesthetized rats caused a hypertensive reaction, while s-nitrosylated Hb derivatives such as SNO-Hb and SNO-PEG-Hb did not raise blood pressure. The plasma half-lives of heme and NO bound to SNO-PEG-Hb were 11.5 and 2.4 hours respectively, indicating that the s-nitrosylated Hb derivative may act as a slow-releasing agent for NO. Based on these findings, SNO-PEG-Hb is a useful candidate for a blood substitute and tool for oxygen therapeutics.
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