Key result
Severe hemorrhage significantly attenuated CCR-mediated inhibition of renal and adrenal sympathetic activity, an effect that was removed by bilateral blockade of adenosine receptors in the caudal NTS.
Adenosine endogenously released into the NTS during severe hemorrhage attenuates cardiopulmonary chemoreflex control of renal and adrenal sympathetic activity.
NTS adenosine may blunt chemoreflex sympathetic inhibition during hemorrhage; hypothesis-generating for reflex control in human hypovolemia.
Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as the exogenous agonists do. Our previous study showed that adenosine is released into the NTS during severe hemorrhage and contributes to reciprocal changes of renal (decreases) and adrenal (increases) sympathetic nerve activity observed in this setting. Both A1 and A2a adenosine receptors are involved. Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control of the two sympathetic outputs is attenuated by adenosine naturally released into the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 μg/kg) under control conditions, during hemorrhage, and during hemorrhage preceded by blockade of NTS adenosine receptors with bilateral microinjections of 8-(p-sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was significantly attenuated during severe hemorrhage despite reciprocal changes in the baseline activity levels, and this attenuation was removed by bilateral blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine endogenously released into the NTS has a similar modulatory effect on integration of cardiovascular reflexes as stimulation of NTS adenosine receptors with exogenous agonists.
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Minić et al. (2014) studied this question. Bilateral microinjections of 8-(p-sulfophenyl) theophylline (adenosine receptor blockade) during severe hemorrhage vs. Control conditions and hemorrhage without blockade was evaluated on Renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide. Severe hemorrhage significantly attenuated CCR-mediated inhibition of renal and adrenal sympathetic activity, an effect that was removed by bilateral blockade of adenosine receptors in the caudal NTS.
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