Modulation of the vagal bradycardia evoked by stimulation of upper airway receptors by central 5‐HT1 receptors in anaesthetized rabbits

Abstract

The effects of central application of 5‐HT_1A and 5‐HT_1B/1D receptor ligands on the reflex bradycardia, apnoea, renal sympathoexcitation and pressor response evoked by stimulating upper airway receptors with smoke in atenolol‐pretreated anaesthetized rabbits were studied. Intracisternal administration of the 5‐HT_1A receptor antagonists WAY‐100635 (100 μg kg⁻¹) and (−)pindolol (100 μg kg⁻¹) significantly reduced the smoke‐induced bradycardia, attenuated the pressor response and in the case of (−)pindolol, sympathetic nerve activity. The same dose of WAY‐100635 i.v. was without effect. Buspirone (200 μg kg⁻¹, i.c.) potentiated the reflex bradycardia. This action was prevented if the animals were pretreated with WAY‐100635 (100 μg kg⁻¹, i.v.) (+)8‐OH‐DPAT (25 μg kg⁻¹, i.c.) attenuated the evoked bradycardia, pressor response, apnoea and renal sympathoexcitation. The attenuation of the apnoea and renal sympathoexcitation, but not the bradycardia or pressor response was prevented in animals pretreated with WAY‐100635 (100 μg kg⁻¹, i.v.). The attenuation of the reflex bradycardia and the reduction in the renal sympathoexcitation were reduced by pretreatment with the 5‐HT_1B/1D receptor antagonist GR127935 (100 μg kg⁻¹, i.v.). In WAY‐100635 (100 μg kg⁻¹, i.v.) pretreated animals, sumatriptan (a 5‐HT_1B/1D receptor agonist) reduced the reflex bradycardia and the pressor response. The 5‐HT_1B/1D receptor antagonist GR127935 (20 μg kg⁻¹, i.c. or 100 μg kg⁻¹, i.v.) had no effect on the reflex responses. In conclusion, the present data are consistent with the hypothesis that activation of central 5‐HT_1A receptors potentiate whilst activation of 5‐HT_1B/1D receptors attenuate the reflex activation of cardiac preganglionic vagal motoneurones evoked by stimulation of upper airway receptors with smoke in rabbits. British Journal of Pharmacology (1998) 125, 409–417; doi:10.1038/sj.bjp.0702085