Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-10-9
pubmed:abstractText
Nitrite reacts with deoxyhemoglobin to generate nitric oxide (NO). This reaction has been proposed to contribute to nitrite-dependent vasodilation in vivo and potentially regulate physiological hypoxic vasodilation. Paradoxically, while deoxyhemoglobin can generate NO via nitrite reduction, both oxyhemoglobin and deoxyhemoglobin potently scavenge NO. Furthermore, at the very low O(2) tensions required to deoxygenate cell-free hemoglobin solutions in aortic ring bioassays, surprisingly low doses of nitrite can be reduced to NO directly by the blood vessel, independent of the presence of hemoglobin; this makes assessments of the role of hemoglobin in the bioactivation of nitrite difficult to characterize in these systems. Therefore, to study the O(2) dependence and ability of deoxhemoglobin to generate vasodilatory NO from nitrite, we performed full factorial experiments of oxyhemoglobin, deoxyhemoglobin, and nitrite and found a highly significant interaction between hemoglobin deoxygenation and nitrite-dependent vasodilation (P < or = 0.0002). Furthermore, we compared the effect of hemoglobin oxygenation on authentic NO-dependent vasodilation using a NONOate NO donor and found that there was no such interaction, i.e., both oxyhemoglobin and deoxyhemoglobin inhibited NO-mediated vasodilation. Finally, we showed that another NO scavenger, 2-carboxyphenyl-4,4-5,5-tetramethylimidazoline-1-oxyl-3-oxide, inhibits nitrite-dependent vasodilation under normoxia and hypoxia, illustrating the uniqueness of the interaction of nitrite with deoxyhemoglobin. While both oxyhemoglobin and deoxyhemoglobin potently inhibit NO, deoxyhemoglobin exhibits unique functional duality as an NO scavenger and nitrite-dependent NO generator, suggesting a model in which intravascular NO homeostasis is regulated by a balance between NO scavenging and NO generation that is dynamically regulated by hemoglobin's O(2) fractional saturation and allosteric nitrite reductase activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1,3-dihydroxy-4,4,5,5-tetramethyl-2-..., http://linkedlifedata.com/resource/pubmed/chemical/1-hexanamine-6-(2-hydroxy-1-methyl-2..., http://linkedlifedata.com/resource/pubmed/chemical/Benzoates, http://linkedlifedata.com/resource/pubmed/chemical/Hemoglobins, http://linkedlifedata.com/resource/pubmed/chemical/Hydrazines, http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors, http://linkedlifedata.com/resource/pubmed/chemical/Nitrite Reductases, http://linkedlifedata.com/resource/pubmed/chemical/Nitrites, http://linkedlifedata.com/resource/pubmed/chemical/Oxygen, http://linkedlifedata.com/resource/pubmed/chemical/Oxyhemoglobins, http://linkedlifedata.com/resource/pubmed/chemical/deoxyhemoglobin
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H2565-72
pubmed:meshHeading
pubmed-meshheading:17766472-Animals, pubmed-meshheading:17766472-Aorta, Thoracic, pubmed-meshheading:17766472-Benzoates, pubmed-meshheading:17766472-Biological Assay, pubmed-meshheading:17766472-Cell Hypoxia, pubmed-meshheading:17766472-Dose-Response Relationship, Drug, pubmed-meshheading:17766472-Hemoglobins, pubmed-meshheading:17766472-Homeostasis, pubmed-meshheading:17766472-Hydrazines, pubmed-meshheading:17766472-Imidazoles, pubmed-meshheading:17766472-Male, pubmed-meshheading:17766472-Models, Cardiovascular, pubmed-meshheading:17766472-Nitric Oxide, pubmed-meshheading:17766472-Nitric Oxide Donors, pubmed-meshheading:17766472-Nitrite Reductases, pubmed-meshheading:17766472-Nitrites, pubmed-meshheading:17766472-Oxygen, pubmed-meshheading:17766472-Oxyhemoglobins, pubmed-meshheading:17766472-Rats, pubmed-meshheading:17766472-Rats, Sprague-Dawley, pubmed-meshheading:17766472-Vasodilation
pubmed:year
2007
pubmed:articleTitle
Hemoglobin oxygen fractional saturation regulates nitrite-dependent vasodilation of aortic ring bioassays.
pubmed:affiliation
Department of Pathology, and Center for Free Radical Biology, University of Alabama at Birmingham, Alabama 35296, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't