Cell-free hemoglobin reverses the endotoxin-mediated hyporesponsivity of rat aortic rings to alpha-adrenergic agents.
Hemoglobin (Hbg) and lysates of red blood cells act as vasoconstrictors in isolated vessels by a mechanism that may involve nitric oxide (NO.) scavenging. To determine if such a mechanism indeed occurs, we investigated the effects of cell-free Hgb, modified Hgp (met Hgb and cyan met Hgb), and red blood cells on the formation of NO. induced by endotoxin in rat aorta. Incubation of rat aortic rings with endotoxin induced a delayed and prolonged release of NO. that resulted in a decrease in the contractile response to phenylephrine. Hgb significantly potentiated contractions to phenylephrine in control rings and also reversed the hyporeactivity to this alpha 1-agonist in endotoxin-treated rings with and without endothelium. Lysed red blood cells but not whole red blood cells shifted the concentration-contraction response curves to phenylephrine significantly to the right in endotoxin-treated preparations. Neither picket-fence porphyrin-albumin (PFP-albumin) or metheme-albumin affected the contractile response to phenylephrine. Oxidation of Hgb to met Hgb did not alter the contractions to an alpha 1-agonist in endotoxin-treated rings. In contrast, the formation of cyan met Hgb abolished the action of Hgb on the vascular reactivity of endotoxin-treated preparations. Together, these results demonstrate that free Hgb can scavenge NO. produced in endotoxin-treated vascular tissue and that the ability to bind NO. requires a cell-free form of Hgb with an intact heme center capable of undergoing redox reactions.
Kilbourn
R G
RG
Department of Genitourinary Oncology, University of Texas M. D. Anderson Cancer Center, Houston.
Joly
G
G
Cashon
B
B
DeAngelo
J
J
Bonaventura
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D004731:Endotoxins / Q000494:pharmacology*; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008706:Methemoglobin / Q000494:pharmacology; D010084:Oxidation-Reduction; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D004731:Endotoxins; D006454:Hemoglobins; D010656:Phenylephrine; D008706:Methemoglobin