Nucleus tractus solitarii A(2a) adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs.
Previously we have shown that stimulation of inhibitory A1 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 A2a adenosine receptors, which dominate over A1 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 A2a receptors may facilitate release of inhibitory transmitters we hypothesized that A2a receptors will act in concert with A1 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 5HT3 receptor agonist, phenylbiguanide, (1-8μg/kg) before and after selective stimulation, blockade or combined blockade and stimulation of NTS A2a adenosine receptors (microinjections into the NTS of CGS-21680 0.2-20pmol/50nl, ZM-241385 40pmol/100nl or ZM-241385+CGS-21680, respectively). We found that stimulation of A2a adenosine receptors uniformly inhibited the regional sympathetic and hemodynamic reflex responses and this effect was abolished by the selective blockade of NTS A2a receptors. This indicates that A2a 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 A2a 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.
Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI 48201, United States.
Zeljka
Z
Minic
Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI 48201, United States.
Donal S
DS
O'Leary
Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI 48201, United States. Electronic address: tscislo@med.wayne.edu.
Tadeusz J
TJ
Scislo
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000311:Adrenal Glands / Q000294:innervation; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D007022:Hypotension / Q000503:physiopathology; D007668:Kidney / Q000294:innervation; D008161:Lumbosacral Region / Q000294:innervation; D008297:Male; D008845:Microinjections; D008959:Models, Neurological; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology; D017552:Solitary Nucleus / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
C547770:Adra2a protein, rat; D001645:Biguanides; D010627:Phenethylamines; D018341:Receptors, Adrenergic, alpha-2; D058827:Serotonin 5-HT3 Receptor Agonists; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine; C008846:phenyl biguanide
Adrenal nerve; Lumbar nerve; Nucleus of the solitary tract; Purinergic receptors; Renal nerve