Purinergic signaling in the retrotrapezoid nucleus (RTN) contributes to central and peripheral chemoreflexes by divergent mechansims

Abstract

Evidence suggests that purinergic signaling in the retrotrapezoid nucleus (RTN) can influence both respiratory and sympathetic activity. Here we evaluate the extent to which purinergic signaling contributes to central and peripheral chemoreception integration at the level of the RTN in vivo. Mean arterial pressure (MAP) and phrenic nerve activity (PNA) were recorded in urethane‐anaesthetized, vagotomized and artificial ventilated male Wistar rats (n = 6–7/group). Bilateral RTN injections of a non‐specific P2‐receptor blocker (PPADS) decreased pressor (8 ± 2 mmHg, vs. saline: 22 ± 4 mmHg) and respiratory (PNA amplitude = 62 ± 3%, vs. saline: 101 ± 5% and PNA frequency = 77 ± 3%, vs. saline: 101 ± 5%) responses to 10% CO2. Conversely, bilateral RTN injections of MRS2179 (P2Y1 receptor antagonist) attenuated cardiorespiratory responses to peripheral chemoreceptor activation, but did not affect CO2‐responsivness. Further, 63% of BDA‐labeled NTS terminals in the RTN are immunoreactive for vesicular glutamate transporter‐2 (VGLUT2) and vesicular nucleotide transporter (VNUT) but only 5% contained glutamic acid decarboxylase‐67 (GAD67). These data indicate that purinergic signaling in the RTN contributes to central and peripheral chemoreception by different, but potentially interactive, mechanisms