Baclofen attenuates cardiorespiratory effects of vagal C fiber stimulation in rats

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Abstract
We tested the hypothesis that γ-aminobutyric acid (GABA) acting on GABAB receptors modulates vagal C fiber mediated reflexes. The effects of a GABAB 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 GABAB 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 GABAB receptors are present on neurons in the medullary pathway of vagal C fibers. In the caudal NTS, GABAB 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 GABAB receptors on the vagal C fiber pathway are not tonically active in rats.Key words: control of breathing, phenyldiguanide, CGP 35348, GABAB receptors, pulmonary chemoreflex.