Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin.
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.
Doherty
D H
DH
Somatogen, Inc. (now known as Baxter Hemoglobin Therapeutics, Inc.), Boulder, CO 80301, USA.
Doyle
M P
MP
Curry
S R
SR
Vali
R J
RJ
Fattor
T J
TJ
Olson
J S
JS
Lemon
D D
DD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016166:Free Radical Scavengers / Q000633:toxicity*; D006454:Hemoglobins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity*; D006973:Hypertension / Q000097:blood / Q000139:chemically induced*; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010108:Oxyhemoglobins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000633:toxicity
D016166:Free Radical Scavengers; D006454:Hemoglobins; D010108:Oxyhemoglobins; D011994:Recombinant Proteins; D009569:Nitric Oxide; C100003:deoxyhemoglobin