| Title | Nitrite Enhances RBC Hypoxic ATP Synthesis and the Release of ATP into the Vasculature: a new mechanism for nitrite induced vasodilation. | | Author(s) | Cao Z, Bell JB, Mohanty JG, Nagababu E, Rifkind JM | | Institution | National Institute on Aging. | | Source | Am J Physiol Heart Circ Physiol 2009 Aug 21. | | Abstract | A role for nitric oxide (NO) produced during the reduction of nitrite by deoxygenated RBCs in regulating vascular dilation has been proposed. It has, however, not been satisfactorily explained how this NO is released from the RBC without first reacting with the large pools of oxyhemoglobin and deoxyhemoglobin in the cell. In this study, we have delineated a mechanism for nitrite induced RBC vasodilation that does not require that NO be released from the cell. Instead we show that nitrite enhances the ATP release from RBCs, which is known to produce vasodilation by several different methods including the interaction with purinergic receptors on the endothelium that stimulate the synthesis of NO by endothelial NO synthase. This mechanism was established in vivo by measuring the decrease in blood pressure when injecting nitrite reacted RBCs into rats. The observed decrease in blood pressure was not observed if e-NOS was inhibited by N-omega-nitro-L-arginine methyl ester (L-NAME) or when any released ATP was degraded by apyrase. The nitrite enhanced ATP release was shown to involve increased binding of nitrite modified hemoglobin to the RBC membrane that displaces glycolytic enzymes from the membrane resulting in the formation of a pool of ATP that is released from the RBC. These results, thus, provide a new mechanism to explain nitrite induced vasodilation. Key words: nitrite reduction, nitric oxide, anerobic glycolysis, hypoxia. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19700624 |
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