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Title
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Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin.
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Authors
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D.H.Doherty,
M.P.Doyle,
S.R.Curry,
R.J.Vali,
T.J.Fattor,
J.S.Olson,
D.D.Lemon.
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Ref.
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Nat Biotechnol, 1998,
16,
672-676.
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PubMed id
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Abstract
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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.
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