Activation of NTS A(1) adenosine receptors inhibits regional sympathetic responses evoked by activation of cardiopulmonary chemoreflex.
Previously we have shown that adenosine operating via the A(1) receptor subtype may inhibit glutamatergic transmission in the baroreflex arc within the nucleus of the solitary tract (NTS) and differentially increase renal (RSNA), preganglionic adrenal (pre-ASNA), and lumbar (LSNA) sympathetic nerve activity (ASNA>RSNA≥LSNA). Since the cardiopulmonary chemoreflex and the arterial baroreflex are mediated via similar medullary pathways, and glutamate is a primary transmitter in both pathways, it is likely that adenosine operating via A(1) receptors in the NTS may differentially inhibit regional sympathetic responses evoked by activation of cardiopulmonary chemoreceptors. Therefore, in urethane-chloralose-anesthetized rats (n = 37) we compared regional sympathoinhibition evoked by the cardiopulmonary chemoreflex (activated with right atrial injections of serotonin 5HT(3) receptor agonist phenylbiguanide, PBG, 1-8 μg/kg) before and after selective stimulation of NTS A(1) adenosine receptors [microinjections of N(6)-cyclopentyl adenosine (CPA), 0.033-330 pmol/50 nl]. Activation of cardiopulmonary chemoreceptors evoked differential, dose-dependent sympathoinhibition (RSNA>ASNA>LSNA), and decreases in arterial pressure and heart rate. These differential sympathetic responses were uniformly attenuated in dose-dependent manner by microinjections of CPA into the NTS. Volume control (n = 11) and blockade of adenosine receptor subtypes in the NTS via 8-(p-sulfophenyl)theophylline (8-SPT, 1 nmol in 100 nl) (n = 9) did not affect the reflex responses. We conclude that activation of NTS A(1) adenosine receptors uniformly inhibits neural and cardiovascular cardiopulmonary chemoreflex responses. A(1) adenosine receptors have no tonic modulatory effect on this reflex under normal conditions. However, when adenosine is released into the NTS (i.e., during stress or severe hypotension/ischemia), it may serve as negative feedback regulator for depressor and sympathoinhibitory reflexes integrated in the NTS.
Department of Physiology, Wayne State University School of Medicine Detroit, Detroit, MI 48201, USA.
Tomoko K
TK
Ichinose
Zeljka
Z
Minic
Cailian
C
Li
Donal S
DS
O'Leary
Tadeusz J
TJ
Scislo
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D001645:Biguanides; D043682:Receptor, Adenosine A1; D017366:Serotonin Receptor Agonists; C048599:N(6)-cyclopentyladenosine; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000241:Adenosine; C008846:phenyl biguanide