Role of the A5 noradrenergic neurons in the control of central chemoreflex in rats

Abstract

Central chemoreflex stimulation produces an increase in breathing and sympathetic discharge. The A5 noradrenergic region project to several brainstem areas involved in autonomic regulation and contributes to the increase in sympathetic discharge elicited by peripheral chemoreflex activation. Here we ask whether the A5 noradrenergic region could contribute to central chemoreflex activation. In urethane anaesthetized sino-aortic denervated and vagotomized male Wistar rats (n = 8/group), hypercapnia (end-expiratory CO2 from 5% to 10%) increased MAP (Δ = +33 ± 4 mmHg), sSNA (Δ = +97 ± 13%), PNA frequency (Δ = +57 ± 11%) and amplitude (Δ = +42 ± 9%). Bilateral injection of muscimol (GABA-A agonist - 100 pmol/50 nl) into the A5 region reduced the rise in MAP (Δ = +19 ± 3 mmHg), sSNA (Δ = +63 ± 5%) and PNA frequency and amplitude (Δ = +38 ± 4% and Δ = +30 ± 6%, respectively) produced by hypercapnia. Bilateral inhibition of A5 region with the immunotoxin anti-dopamine β-hydroxylase-saporin (anti-DβH-SAP) reduced the increase in MAP (Δ = +22 ± 3 mmHg), sSNA (Δ = +68 ± 9%) and PNA amplitude (Δ = +33 ± 7%, respectively). The results suggest that A5 noradrenergic neurons contribute to the increase in MAP, sSNA and PNA activation during central chemoreflex stimulation. Financial support: FAPESP (06/60174-9 to TSM, 09/13333-9 to CLT).