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Influence of Oxygen on Adenosine A1 and A2a Receptor Gene Expression in Cerebral Blood Vessels of Sprague-Dawley Rats

Introduction: Hyperbaric oxygenation (HBO2) has the ability to alter protein expression, modulates signaling pathways, and influences vascular structure and function leading to changes in vasomotor responses. Adenosine receptors (AR) play an important role in the mechanism of action of oxygen as a vasoactive substance, the expression of which differs significantly between cell types. The aim of this study was to determine the expression of adenosine receptors' (A1R and A2aR) in cerebral blood vessels of Sprague-Dawley rats exposed to acute and intermittent HBO2. Methods: Male and female healthy Sprague-Dawley rats (N=18), 8-10 weeks old were divided into 3 groups: CTRL (control non-HBO2), A-HBO2 (exposed to single HBO2 at a pressure od 2 bars/ 2 hours) and 4D-HBO2 (animals exposed to HBO2 for 2 hours daily for 4 days, with sample isolation on 5th day). The rats were anesthetized with ketamine- chloride (3 ml/kg) and midazolam (0, 5 ml/kg) and decapitated. Afterwards, samples of surface brain blood vessels were used for qRT-PCR. Relative gene expression of A1R and A2aR genes was measured with HPRT1 as the housekeeping gene. Results: Acute exposure to HBO2 did not significantly alter A1R or A2aR gene expression. There was a significant increase in A1R i A2aR expression in the 4D-HBO2 group compared to CTRL. Discussion: High oxygen concentrations during HBO2 lead to changes in vascular reactivity mechanism. Adenosine A2aR are known to mediate a protective compensatory vasodilatory response to tissue hypoxia. Although A1R activation is known to cause vasoconstriction, some studies suggest that during hypoxia, A1R protects tissue from damage by reducing levels of ischemic mediator and by causing vasodilation. In addition, A1R can modulate A2aR expression. Also, A1R are known to be more sensitive to hypoxia. Conclusion: Intermittent exposure to hyperbaric oxygen acts as pseudohypoxia, resulting in a protective compensatory increase in adenosine A1R and A2aR gene expression.

hyperbaric oxygenation, adenosine receptors, cerebral blood vessels, gene expression, Sprague-Dawley rats

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