Baroreceptor-mediated inhibition of respiration after peripheral and central administration of a 5-HT1A receptor agonist in neonatal piglets

Abstract

Inhibition of neurones in the ventral medulla accentuates the respiratory inhibition associated with acute blood pressure elevation in piglets. Activation of presynaptic 5-HT1A receptors inhibits serotonergic neurones in the ventral medulla and caudal raphé, and we tested the hypothesis that administration of 8-hydroxydipropylaminotetralin (8-OH-DPAT), a 5-HT 1A agonist, within the rostroventral medulla and caudal raphé would enhance baroreceptor-mediated inhibition of respiratory activity in decerebrate, neonatal piglets. Baroreceptor stimulation was achieved by inflating a balloon in the distal aorta to elevate carotid blood pressure. After two to four control trials of baroreceptor stimulation, each piglet was given either a single intravenous (i.v.) dose of 10 μg kg-1 8-OH-DPAT or treated by adding 10 or 30 mm 8-OH-DPAT to the dialysate for ∼10 min to inhibit serotonergic neurones, after which the baroreceptor stimulation trials were repeated. Baroreceptor stimulation reduced respiratory activity, particularly the respiratory frequency, which diminished from 35.7 ± 3.3 to 33.8 ± 3.1 breaths min-1 (P < 0.02) and, following i.v. 8-OH-DPAT, baroreceptor-mediated inhibition of respiratory output was significantly accentuated (P < 0.05); the respiratory frequency declined from 34.5 ± 3.6 to 26.5 ± 2.9 breaths min-1. Increasing aortic blood pressure reduced the respiratory frequency (P < 0.01), but focal dialysis of 10 or 30 mm 8-OH-DPAT had, on average, no effect on the ventilatory inhibition associated with an acute elevation of blood pressure. We conclude that activation of 5-HT1A receptors after systemic administration of 8-OH-DPAT enhanced baroreflex-mediated inhibition of ventilation, but this effect cannot be attributed to 5-HT1A receptor activation within the rostroventral medulla and caudal raphé. © 2007 The Authors.