Baclofen-induced block of the Hering–Breuer expiratory-promoting reflex in rats

Abstract

Baclofen, a gamma-aminobutyric acid (GABA) agonist acting on GABAB receptors, has profound effects on respiratory function. We tested a hypothesis that GABAB receptors are involved in modulation of the respiratory reflexes mediated by pulmonary slowly adapting stretch receptors. Urethane-anesthetized (1.2-1.6 g/kg; i.p.) Wistar rats with body weight 230-320 g were breathing room air supplemented with oxygen. The gas mixture was applied to the T-shaped tracheal cannula at a flow rate of 1.5 L/min. The head of the animals was mounted in a stereotaxic apparatus, and the medulla was exposed. We recorded integrated diaphragmatic EMG (Di) and tracheal and arterial blood pressures. Injections of 100 nL of saline into the nucleus tractus solitarii (NTS) preceded injections of 60 or 110 pmol baclofen in group 1 (n = 14), and 2.8 nmol CGP 35348, a GABAB receptor antagonist, in group 2 (n = 5). Saline had no effects on baseline Di. Occlusion of the tracheal cannula caused an increase in tracheal pressure to 8 cmH2O (1 cmH2O = 98.1 Pa) and provoked a prolongation of expiration (the Hering-Breuer expiratory-promoting reflex) in all drug-free rats. Baclofen abolished the Hering-Breuer reflex in all rats. CGP 35348 reversed the block of the reflex. In group 2, CGP 35348 prevented the effects of baclofen, and alone did not affect respiration. These results support our hypothesis and suggest that GABAB receptors are present on the medullary pathway of slowly adapting mechanoreceptor input. However, GABAB receptors in the rat NTS may not be involved in modulation of the fundamental respiratory function.