title: Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors.
abstract: 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.
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Zeljka
authors: Z
authors: Minic
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Cailian
authors: C
authors: Li
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Donal S
authors: DS
authors: O'Leary
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan tscislo@med.wayne.edu.
authors: Tadeusz J
authors: TJ
authors: Scislo
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000311:Adrenal Glands / Q000294:innervation; D000818:Animals; D001794:Blood Pressure; D002319:Cardiovascular System / Q000294:innervation*; D002628:Chemoreceptor Cells / Q000378:metabolism*; D004195:Disease Models, Animal; D006339:Heart Rate; D006470:Hemorrhage / Q000378:metabolism* / Q000503:physiopathology; D007022:Hypotension / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000294:innervation; D008297:Male; D009433:Neural Inhibition; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology; D012720:Severity of Illness Index; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D000241:Adenosine
keywords: adenosine receptor antagonist; adrenal nerve; nucleus of the solitary tract; purinergic receptors; renal nerve