Hemoglobin as a (glutathione-dependent?) nitrite reductase: a vasodilation study
Angela Fago1, Thomas Dalsgaard1,2 and Ulf Simonsen2
1Zoophysiology, Institute of Biology, University of Aarhus
2Institute of Pharmacology, University of Aarhus
(e-mail:
[email protected])
Hemoglobin (Hb) has been recently proposed as an alternative source for vasoactive NO to mediate vasodilation and augument blood flow under hypoxic conditions. According to two current hypotheses, at low oxygen tensions of the blood NO can either: 1) be released by S-nitrosylated Hb (SNO-Hb) during the R-T allosteric transition (1), or 2) be generated from nitrite in a reaction catalyzed by deoxygenated T-state Hb (2;3). However, in the course of the Hb-catalyzed nitrite reduction strong S-nitrosating agents (including NO+) are also produced (4), whereby SNO-dependent pathways may contribute to the observed hypoxic vasodilation.
Using a wire myograph we have investigated hypoxic vasodilation of rat aorta segments in the presence of Hb at various concentrations of sodium nitrite, with and without added inositol hexakiphosphate (IHP), to trigger the conversion of Hb from the R to the T conformational state, and with and without added glutathione (GSH), to assess the contribution of S-nitrosylation pathways. During the experiments endothelial NO production of the tissue was inhibited by asymmetric dimethyl-arginine.
Albeit less efficiently than other vasodilators (including S-nitrosylated glutathione, GSNO), nitrite alone is able to induce vasodilation in a concentration-dependent fashion, thus supporting earlier work. Such vasodilation, however, does not seem to be significntly affected by the presence of Hb, either in the presence or in the absence of IHP. Conversely, in the presence of GSH, nitrite-dependent vasodilation significantly increases under conditions favouring the T-state of the Hb (+IHP), thus indicating that vasoactive SNO-compounds are generated in the reaction between T-state Hb and nitrite.
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2. Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., Huang, K. T., Shields, H., Kim-Shapiro, D. B., Schechter, A. N., Cannon, R. O., and Gladwin, M. T. (2003) Nat Med 9, 1498-1505
3. Nagababu, E., Ramasamy, S., Abernethy, D. R., and Rifkind, J. M. (2003) J. Biol. Chem 278, 46349-46356
4. Robinson, J. M. and Lancaster, J. R., Jr. (2005) Am. J. Respir. Cell Mol. Biol. 32, 257-261
| Periode | 28 sep. 2005 |
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| Begivenhedstitel | What's new in oxygen binding heme proteins and red blood cell physiology |
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| Begivenhedstype | Konference |
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| Placering | Århus, DanmarkVis på kort |
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