CHANGES OF VASCULAR REACTIVITY TO ADENOSINE A1 AND A2A RECEPTOR AGONISTS AFTER HYPERBARIC OXYGENATION

Abstract

Objective: Hyperbaric oxygenation (HBO) affects vascular reactivitiy, which plays an important role in the pathophysiology of hypertension and other cardiovascular diseases. New data suggest important effects of HBO on oxidative stress and alteration of production of vasoactive metabolites in blood vessels; however, the role of adenosine A1 and A2a receptors is still underinvestigated.This study aimed to determine the functional role of adenosine A1 and A2a receptors in changes of vascular reactivity in isolated middle cerebral arteries (MCA) of Spague-Dawley rats, after acute and intermittent HBO. Design and method: Male and female healthy Sprague-Dawley rats aged 8–10 weeks were divided into 3 groups: CTRL (control non HBO), A-HBO (single animals exposed to HBO for 2 hours) and 4D-HBO (animals exposed to HBO at a pressure od 2 bars for 2 hours daily for 4 days, with vascular experiments conducted on the fifth day). The rats were anesthetized with ketamine-chloride (3 ml/kg) and midazolam (0,5 ml/kg) and decapitated. The MCA were isolated, cannulated and pressurized for 60’at 80 mmHg to assess basal diameter using pressure myograph Danish Myo Technology. A1 adenosin receptor selective agonist CCPA or A2a adenosin receptor agonist CGS in concentrations from 10–5 to 10–10 M were added to the vessel chamber, and blood vessel diameter was measured after incubation of the drug for 15 minutes. Statistical analyses were performed with Two-way ANOVA tests; p < 0.05 was considered significant. Results: The vasoconstriction in response to A1 agonist administration was similar between the CTRL and 4D-HBO group, while it was significantly reduced in A-HBO compared to the CTRL and 4D-HBO groups. The vasodilation in response to A2a stimulation was significantly reduced in rats exposed to A-HBO and I-HBO compared to CTRL at higher drug concentrations (10–7 to 10–5 M). Conclusions: Acute exposure of rats to HBO leads to decrease in the vasoconstrictive response to adenosine A1 receptor stimulation, while acute and intermittent exposure of rats to HBO is associated with a decrease in the vasodilatory response of MCA to adenosine A2a receptor activation, suggesting that HBO alters sensitivity to or expression of receptors.