Adjustments in purinergic metabolism maintain the contribution of adenosine and ATP to carotid body chemosensory activity in ageing

Physiology 2019 (Aberdeen, UK) (2019) Proc Physiol Soc 43, C012

Oral Communications: Adjustments in purinergic metabolism maintain the contribution of adenosine and ATP to carotid body chemosensory activity in ageing

S. Conde1, M. J. Ribeiro1, J. Prieto-Lloret1, B. F. Melo1, E. C. Monteiro1, J. F. Sacramento1

1. CEDOC, NOVA Medical School, Lisboa, Portugal.

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Adenosine and ATP are key neurotransmitters involved in carotid body (CB) response to hypoxia (1). CB exhibits a decline in its functionality in ageing (2), however, several diseases associated with ageing present increased CB activity (3,5). Here the effect of ageing was investigated on characteristics involved in CB function and on the contribution of adenosine and ATP to CB chemosensory activity. Experiments were performed in 3 and 24 months male Wistar rats anesthetized with pentobarbitone (60 mg/kg, ip). Ageing was investigated on: the number of type 1 and type 2 CB cells; the expression of SNAP25, tyrosine hydroxylase (TH), CD73 and ENT1 transporter in the CB and of A2A adenosine and P2X2 ATP receptors in the petrosal ganglion; CB basal and hypoxic release of adenosine and ATP; the contribution of adenosine and ATP to carotid sinus nerve (CSN) electrophysiological responses to hypoxia and hypercapnia and on spontaneous ventilation and in response to ischemic hypoxia by occlusion of the carotid common artery (OCC). Student t-test and one- and two-way Anova tests were used. Ageing decreased by: 49.0% TH immune-positive cells (p<0.01), but not the number of type 2 cells; 52.5% and 42.2% the expression of P2X2 and A2A receptors in petrosal ganglion; 46.7%(p<0.05), 56.2%(p<0.01) and 68.1%(p<0.001), the basal and 10 and 2%O2-hypoxic release of ATP (3M 20%O2=5.1±0.8 pmol/CB; 10%O2=9.6±1.5 pmol/CB; 2%O2=18.0±2.0 pmol/CB); 97.5%(p<0.001), 98.2%(p<0.001), and 98.1%(p<0.001) the basal and 10 and 2%O2-hypoxic release of adenosine (3M 20%O2=25.8±3.9 pmol/CB; 10%O2=62.8±6.2 pmol/CB; 2%O2=43.8±4.9 pmol/CB) from CB. Ageing increased by 87.1% CD73 immune-positive cells (p<0.01) and by 83.7% and 400.5% the expression of SNAP25 (p<0.01) and ENT1 (p<0.01) in the CB. Ageing did not modify basal CSN activity (basal activity: 3M=2.2±0.4 spikes/s; 24M=1.9±0.2 spikes/s) or the activity in response to hypercapnia, but decreased by 77.8% (p<0.01), 67.8% (p<0.001) and 51.9%(p<0.001) the CSN-electrophysiological activity in response to 7%O2, 5%O2 and 0%O2. Bilateral OCCs during 5, 10 and 15s induced an increase in ventilation proportional to the duration of ischemia (OCC 5s=59.8±4.2%; OCC 10s=139.8±10.6%; OCC 15s=23.9±15.2%), an effect decreased by ageing. ATP contributes with ≈50% to the ventilatory responses to all ischemic intensities tested in young and in aged rats; the contribution of adenosine was dependent on the intensity of ischemia, being maximal in ischemias of 5s (50%) and much smaller in 15s ischemias. Our results demonstrate that although ageing decrease the number of type 1 cells in the CB, this seems to impact only in the responses to hypoxia, and not on CB basal and hypercapnic activity. Additionally, both ATP and adenosine, contribute to CB chemosensory activity in ageing. Though CB function in response to hypoxia decreases with age the relative contribution of both ATP and adenosine for CB activity is maintained.



Where applicable, experiments conform with Society ethical requirements.

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