Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin

Nat Biotechnol. 1998 Jul;16(7):672-6. doi: 10.1038/nbt0798-672.


Administration of extracellular hemoglobin-based oxygen carriers often induces mild increases in blood pressure. In order to test whether nitric oxide (NO) scavenging is responsible for the hypertensive effect, we constructed and tested a set of recombinant hemoglobins that vary in rates of reaction with NO. The results suggest that the rapid reactions of oxy- and deoxyhemoglobin with nitric oxide are the fundamental cause of the hypertension. The magnitude of the blood-pressure effect correlates directly with the in vitro rate of NO oxidation. Hemoglobins with decreased NO-scavenging activity may be more suitable for certain therapeutic applications than those that cause depletion of nitric oxide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Free Radical Scavengers / toxicity*
  • Hemoglobins / administration & dosage
  • Hemoglobins / genetics
  • Hemoglobins / metabolism*
  • Hemoglobins / toxicity*
  • Hypertension / blood
  • Hypertension / chemically induced*
  • Male
  • Nitric Oxide / blood
  • Nitric Oxide / metabolism*
  • Oxygen Consumption / drug effects
  • Oxyhemoglobins / chemistry
  • Oxyhemoglobins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / toxicity


  • Free Radical Scavengers
  • Hemoglobins
  • Oxyhemoglobins
  • Recombinant Proteins
  • Nitric Oxide
  • deoxyhemoglobin