Role of A5 noradrenergic neurons in the chemoreflex control of respiratory and sympathetic activities in unanesthetized conditions

Abstract

The A5 area at the ventrolateral pons contains noradrenergic neurons connected with other medullary areas involved in the cardiorespiratory control. Its contribution to the cardiorespiratory regulation was previously evidenced in anesthetized conditions. In the present study, we investigated the involvement of the A5 noradrenergic neurons to the basal and chemoreflex control of the sympathetic and respiratory activities in unanesthetized conditions. A5 noradrenergic neurons were lesioned using microinjections of anti-dopamine β-hydroxylase saporin (anti-DβH-SAP). After 7–8 days, we evaluated the arterial pressure levels, heart rate and minute ventilation in freely moving adult rats (280–350 g) as well as recorded from thoracic sympathetic (tSN) and phrenic nerves (PN) using the arterially perfused in situ preparation of juvenile rats (80–90 g). Baseline cardiovascular, sympathetic and respiratory parameters were similar between control (n = 7–8) and A5-lesioned rats (n = 5–6) in both experimental preparations. In adult rats, lesions of A5 noradrenergic neurons did not modify the reflex cardiorespiratory adjustments to hypoxia (7% O2) and hypercapnia (7% CO2). In the in situ preparations, the sympatho-excitation, but not the PN reflex response, elicited by either the stimulation of peripheral chemoreceptors (ΔtSN: 110 ± 12% vs 58 ± 8%, P < 0.01) or hypercapnia (ΔtSN: 9.5 ± 1.4% vs 3.9 ± 1.7%, P < 0.05) was attenuated in A5-lesioned rats compared to controls. Our data demonstrated that A5 noradrenergic neurons are part of the circuitry recruited for the processing of sympathetic response to hypoxia and hypercapnia in unanesthetized conditions.

Brainstem catecholaminergic neurones and breathing control during postnatal development in male and female rats

“…Indeed, in a recent study, adult and juvenile rats with specific lesions of A5 neurones showed normal respiratory frequencies that were unaffected by the A5 lesion (Taxini et al . ), with the same findings being observed after A6 noradrenergic lesions (Biancardi et al . ).…”

“…In agreement, the A5 inhibitory role on the respiratory rhythm generator appears to be stronger at birth than it is after a few postnatal days . Indeed, in a recent study, adult and juvenile rats with specific lesions of A5 neurones showed normal respiratory frequencies that were unaffected by the A5 lesion (Taxini et al 2017), with the same findings being observed after A6 noradrenergic lesions (Biancardi et al 2008). Accordingly, it appears that the role of noradrenergic neurones on basal ventilation is more prominent in early neonatal stages.…”

Mapping of the excitatory, inhibitory, and modulatory afferent projections to the anatomically defined active expiratory oscillator in adult male rats

“…We also found primarily ipsilateral inhibitory and excitatory contralateral GFP + neurons in the slightly more rostral and diffuse A5 area. Noradrenergic A5 neurons contribute to hypercapnic and hypoxic ventilatory responses (Guyenet, Koshiya, Huangfu, Verberne, & Riley, 1993; Kanbar, Depuy, West, Stornetta, & Guyenet, 2011; Taxini et al, 2017; Taxini, Takakura, Gargaglioni, & Moreira, 2011), but none of the A5 GFP + neurons were noradrenergic (i.e., they were all TH − ), which precludes us from making any prediction that these cathecolaminergic cells contribute to homeostatic respiratory reflexes by acting on pFRG/pF L .…”

High-fat diet increases respiratory frequency and abdominal expiratory motor activity during hypercapnia

“…In the next day, ventilation and cardiovascular measurements were performed in conscious, freely moving rats. The pulmonary ventilation (V E ) was measured during normoxia, hypoxia (7% O 2 + N 2 balance) and hypercapnia (7% CO 2 + 21% O 2 + N 2 balance) conditions, as previously described (Bassi et al, 2015; Taxini et al, 2017) and baroreflex was tested by i.v. administration of phenylephrine (5 μg/kg of b.…”