Baclofen attenuates cardiorespiratory effects of vagal C fiber stimulation in rats.
We tested the hypothesis that gamma-aminobutyric acid (GABA) acting on GABA B receptors modulates vagal C fiber mediated reflexes. The effects of a GABA B receptor agonist, (-)-baclofen, injected bilaterally into the nucleus tractus solitarius (NTS), on the cardiorespiratory response to C fiber stimulation with phenyldiguanide (PDG) introduced into the right atrium were evaluated in urethane-anesthetized Wistar rats. We recorded integrated diaphragmatic EMG (Di) and mean arterial blood pressure (ABP). Before injections of baclofen into the NTS, PDG caused bradycardia, hypotension, and apnea, followed by a decrease in Di amplitude and variable changes in respiratory timing. Only injections of baclofen at 0.6 mm caudal to the obex reduced or prevented the PDG-evoked apnea. In contrast, independent of site of injection baclofen diminished bradycardia and the decrease in Di in postapnea breaths. The ABP response to PDG was never affected by baclofen. A GABA B receptor antagonist, CGP 35348, fully restored the responses to PDG, but CGP 35348 alone did not affect the responses to PDG. Our results suggest that GABA B receptors are present on neurons in the medullary pathway of vagal C fibers. In the caudal NTS, GABA B receptors modulate the PDG-evoked apnea, and within the larger area of the NTS these receptors modulate bradycardia and postapnea patterns of breathing. The absence of effects of CGP 35348 alone implies that GABA B receptors on the vagal C fiber pathway are not tonically active in rats.
Seifert
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Department of Physiology, McGill University, Montreal, Canada.
Trippenbach
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D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001645:Biguanides / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014630:Vagus Nerve / Q000187:drug effects*
D001645:Biguanides; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D017366:Serotonin Receptor Agonists; C066430:CGP 35348; D001418:Baclofen; C008846:phenyl biguanide