title: Ferrrous hemoglobin scavenging of endothelium derived nitric oxide is a principal mechanism for hemoglobin mediated vasoactivities in isolated rat thoracic aorta.
abstract: The exact mechanism of hemoglobin (Hb) associated vasoconstriction has not been elucidated. We investigated this problem using isolated superfused rat aortic rings with intact endothelium. Human stroma-free hemoglobin solution (SFH) at 2uM reversed vaso relaxation induced by 33uM acetylcholine (Ach). Further, pretreatment with 4uM SFH inhibited Ach(333uM) induced dilation. The SFH induced contraction was reversible by glyceryltrinitrate (GTN), a nitric oxide (NO) donor. Preincubation with a NO synthase inhibitor nitro-L-arginine-methyl ester (NAME, 0.4nM) caused almost complete inhibition of the Hb vasoactivity. Unlike SFH (ferrous oxyHb), prenitrosylated SFH (HbNO) or ferric Hb derivatives (e.g., metHb, HbCN) did not elicit vasoconstriction. The presence of 2uM SFH did not significantly reduce the vasodilatory effectiveness of endothelium independent vasodilators isoproteranol (ISO) and papaverine (PPV). These results suggest that a primary mechanism for Hb vasoconstrictor activity is ferrous Hb scavenging of endothelium derived NO, a signal for guanylate cyclase-cGMP mediated smooth muscle relaxation. Additionally, it appears that the Hb induced vasoactivities may be modulated with NO independent vasodilators.
authors.affiliation: Department of Surgery, Miriam Hospital, Providence, RI 02906, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Kim
authors.forename: A G
authors.initials: AG
authors.lastname: Greenburg
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000378:metabolism; D010952:Plasma Substitutes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006454:Hemoglobins; D008024:Ligands; D010108:Oxyhemoglobins; D010952:Plasma Substitutes; D014662:Vasoconstrictor Agents; C016484:hemoglobin, stroma free; D009569:Nitric Oxide; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine