Cardiovascular and respiratory evaluation in adenosine A_2A receptor knockout mice submitted to short-term sustained...

Sustained hypoxia (SH) in mice induces changes in the respiratory pattern and increase in the parasympathetic tone to the heart. Among adenosine G-protein-coupled receptors (GPCRs), the A_2A receptors are especially important in mediating adenosine actions during hypoxia due to their expression in neurons involved with the generation and modulation of the autonomic and respiratory functions. Herein, we performed an in vivo evaluation of the baseline cardiovascular and respiratory parameters and their changes in response to SH in knockout mice for A_2A receptors (A_2A KO). SH produced similar and significant reductions in mean arterial pressure and heart rate in both wild-type (WT) and A_2A KO mice when compared to their respective normoxic controls. Mice from WT and A_2A KO groups submitted to normoxia or SH presented similar cardiovascular responses to peripheral chemoreflex activation (KCN). Under normoxic conditions A_2A KO mice presented a respiratory frequency (f_R ) significantly higher in relation to the WT group, which was reduced in response to SH. These data show that the lack of adenosine A_2A receptors in mice does not affect the cardiovascular parameters and the autonomic responses to chemoreflex activation in control (normoxia) and SH mice. We conclude that the A_2A receptors play a major role in the control of respiratory frequency and in the tachypnoeic response to SH in mice. NEW FINDINGS: What is the central question of this study? Are cardiovascular and respiratory parameters and their changes in response to sustained hypoxia (SH) altered in adenosine A_2A receptor knockout mice? What is the main finding and its importance? Cardiovascular parameters and their changes in response to SH were not altered in A_2A KO mice. The respiratory frequency in A_2A KO was higher than in WT mice. In response to SH the respiratory frequency increased in WT, while it was reduced in A_2A KO mice. A_2A receptors play a major role in the modulation of respiratory frequency and in the tachypnoeic response to SH in mice.