Cardiovascular and respiratory profile of adenosine A 2A receptors knockout mice submitted to sustained hypoxia

Abstract

Taking into consideration the relevance of adenosine as a signaling molecule during hypoxic challenges and the evidence of an important role of A2A receptors regions of the brainstem involved with the generation and modulation of the autonomic and respiratory functions, in the present study we evaluated the cardiovascular and respiratory changes in response to sustained hypoxia (SH) in knockout mice for A2A receptors (A2AKO). For this, we used male A2AKO and male Balb/c wild-type (WT) mice as a control. Under anesthesia, catheters were inserted into the femoral artery, for recording arterial pressure (MAP), and jugular vein for drug injection. Four days after, mice were submitted to normoxia or SH (24h, FiO2 0.1). At the end of these protocols, cardiovascular and respiratory parameters were recorded. Peripheral chemoreflex was activated by potassium cyanide (KCN, 0,16 mg/Kg, iv). In distinct groups of A2AKO and WT mice, with the femoral artery previously catheterized, respiratory parameters were evaluated before and after SH using whole-body plethysmography. At the end of respiratory recordings, a sample of arterial blood was collected for arterial blood gases analysis. Similar and ignificant reductions in MAP and heart rate (HR) were observed in WT [(102±5 vs 109±6 mmHg, P=0.0172), (329±31 vs 441±55 bpm, P<0.0001)] and A2AKO [(104±5 vs 111±7 mmHg; P=0.0141), (318±59 vs 408±64 bpm, P=0.0006)] mice submitted to SH when compared to their respective normoxia controls (WT: n=11; A2AKO: n=13). Mice from control and A2AKO groups presented similar cardiovascular responses to KCN in normoxic as well as in hypoxic conditions. Under normoxic conditions, A2AKO mice (n=11) presented significant increase in respiratory frequency (241 ± 25 vs 184 ± 11 breaths.min-1, P < 0.0001) when compared to respective genetic controls (n=8). Both A2AKO [(24±3 vs 32± 2 mmHg; P<0.0001), (105±6 vs 90±4 mmHg, P = 0.0002)] and WT [(23±4 vs 32±3 mmHg, P<0.0001), (100±9 vs 88±10 mmHg, P=0.0034)] mice presented a significant reduction in pCO2 and an increase in pO2 after SH. The data are showing that the lack of adenosine A2A receptors does not affect the autonomic responses to chemoreflex activation, but are relevant in modulating respiratory activity in normal mice since in the A2AKO mice it was observed a significant increase in respiratory frequency. The data also suggest that A2A receptors play no major role in autonomic and respiratory changes in mice submitted to SH. FAPESP (2018/15957-2 and 2021/01767-0) and CNPQ (309338/2020-4). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.