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Modeling hemoglobin nitrite reductase activity as a mechanism of hypoxic vasodilation?

Rong, Z and Cooper, CE (2013) 'Modeling hemoglobin nitrite reductase activity as a mechanism of hypoxic vasodilation?' Advances in Experimental Medicine and Biology, 789. 361 - 368. ISSN 0065-2598

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Abstract

The brain's response to hypoxia is to increase cerebral blood flow (CBF). However, the molecular mechanism underpinning this phenomenon is controversial. We have developed a model to simulate brain blood flow and oxygen metabolism called BRAINSIGNALS. This model is primarily designed to assist in the interpretation of multimodal noninvasive clinical measurements. However, we have recently used this model to test the feasibility of a range of molecular mechanisms proposed to explain hypoxic vasodilation. An increase in the concentration of the vasodilator nitric oxide (NO) at low pO<inf>2</inf> is a feature of many such mechanisms. One model suggests that mitochondrial cytochrome c oxidase (CCO) catalyzes the metabolism of NO. This metabolism declines at low pO<inf>2</inf>, resulting in an increase in the steady-state levels of NO and a consequent increase in CBF. Using BRAINSIGNALS we were able to model this effect. However, the increases in NO and CBF occurred at far lower pO<inf>2</inf> values than predicted from physiological data (Rong et al. 2013 Adv Exp Med Biol. 765, 231-238). The aim of the present study was to test an alternative mechanism, one that actively generates NO as pO<inf>2</inf> drops, namely, the reduction of nitrite to NO by deoxyhemoglobin. In this mechanism, NO synthesis has a maximum of NO production near the hemoglobin p50. The addition of this mechanism resulted in a significantly better fit to the experimental data of the CBF(PaO<inf>2</inf>) curve. © 2013 Springer Science+Business Media New York.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Depositing User: Users 161 not found.
Date Deposited: 16 Sep 2014 09:25
Last Modified: 01 Aug 2019 21:17
URI: http://repository.essex.ac.uk/id/eprint/10201

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