Cardiovascular and respiratory evaluation in adenosine A2A receptor knockout mice submitted to short‐term sustained hypoxia

Abstract

AbstractSustained 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 A2A 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 A2A receptors (A2AKO). SH produced similar and significant reductions in mean arterial pressure and heart rate in both wild‐type (WT) and A2AKO mice when compared to their respective normoxic controls. Mice from WT and A2AKO groups submitted to normoxia or SH presented similar cardiovascular responses to peripheral chemoreflex activation (KCN). Under normoxic conditions A2AKO mice presented a respiratory frequency (fR) significantly higher in relation to the WT group, which was reduced in response to SH. These data show that the lack of adenosine A2A 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 A2A receptors play a major role in the control of respiratory frequency and in the tachypnoeic response to SH in mice.