Nucleus tractus solitarii A(2a) adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs

作者：Minic Zeljka; O'Leary Donal S; Scislo Tadeusz J^*

来源：Autonomic Neuroscience-Basic & Clinical, 2014, 180: 32-42.

DOI：10.1016/j.autneu.2013.10.005

• Nucleus of the solitary tract
• Purinergic receptors
• Renal nerve
• Adrenal nerve
• Lumbar nerve

Previously we have shown that stimulation of inhibitory A(1) adenosine receptors located in the nucleus tractus solitarii (NTS) attenuates cardiopulmonary chemoreflex (CCR) evoked inhibition of renal, adrenal and lumbar sympathetic nerve activity and reflex decreases in arterial pressure and heart rate. Activation of facilitatory A(2a) adenosine receptors, which dominate over A(1) receptors in the NTS, contrastingly alters baseline activity of regional sympathetic outputs: it decreases renal, increases adrenal and does not change lumbar nerve activity. Considering that NTS A(2a) receptors may facilitate release of inhibitory transmitters we hypothesized that A(2a) receptors will act in concert with A(1) receptors differentially inhibiting regional sympathetic CCR responses (adrenal > lumbar > renal). In urethane/chloralose anesthetized rats (n = 38) we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of serotonin 5HT(3) receptor agonist, phenylbiguanide, (1-8 mu/kg) before and after selective stimulation, blockade or combined blockade and stimulation of NTS A(2a) adenosine receptors (microinjections into the NTS of CGS-21680 0.2-20 pmol/50 nl, ZM-241385 40 pmol/100 nl or ZM-241385 + CGS-21680, respectively). We found that stimulation of A(2a) adenosine receptors uniformly inhibited the regional sympathetic and hemodynamic reflex responses and this effect was abolished by the selective blockade of NTS A(2a) receptors. This indicates that A(2a) receptor triggered inhibition of CCR responses and the contrasting shifts in baseline sympathetic activity are mediated via different mechanisms. These data implicate that stimulation of NTS A(2a) receptors triggers unknown inhibitory mechanism(s) which in turn inhibit transmission in the CCR pathway when adenosine is released into the NTS during severe hypotension.

• 出版日期2014-2