NTS adenosine A2a receptors inhibit the cardiopulmonary chemoreflex control of regional sympathetic outputs via a GABAergic mechanism.

Adenosine is a powerful central neuromodulator acting via opposing A1 (inhibitor) and A2a (activator) receptors. However, in the NTS both adenosine receptor subtypes attenuate cardiopulmonary chemoreflex (CCR) sympathoinhibition of renal, adrenal and lumbar sympathetic nerve activity and attenuate reflex decreases in arterial pressure and heart rate. A1 receptors inhibit glutamatergic transmission in the CCR pathway whereas A2a receptors most likely facilitate release of unknown inhibitory neurotransmitter which in turn inhibits the CCR. We hypothesized that A2a adenosine receptors inhibit the CCR via facilitation of GABA release in the NTS. In urethane/chloralose anesthetized rats (n=51) we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of serotonin 5HT3 receptor agonist, phenylbiguanide, (PBG 1-8 μg/kg) before and after selective stimulation of NTS A2a adenosine receptors (microinjections into the NTS of CGS-21680 20 pmol/50 nl) preceded by blockade of GABAA or GABAB receptors in the NTS (bicuculline 10 pmol /100 nl, or SCH-50911, 1 nmol/100 nl). Blockade of GABAA receptors virtually abolished A2a mediated inhibition of the CCR. GABAB receptors had much weaker but significant effects. These effects were similar for the different sympathetic outputs. We conclude that stimulation of NTS A2a adenosine receptors inhibits CCR evoked hemodynamic and regional sympathetic reflex responses via a GABA-ergic mechanism. [ABSTRACT FROM AUTHOR]

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