Purinergic receptor blockade in the retrotrapezoid nucleus attenuates the respiratory chemoreflexes in awake rats

Abstract

AIM Recent evidence suggests that ATP-mediated purinergic signaling at the level of the rostral ventrolateral medulla (RVLM) contributes to both central and peripheral chemoreceptor control of breathing and blood pressure: neurons in the retrotrapezoid nucleus (RTN) function as central chemoreceptors in part by responding to CO2-evoked ATP release by activation of yet unknown P2 receptors, and nearby catecholaminergic C1 neurons regulate blood pressure responses to peripheral chemoreceptor activation by a P2Y1 receptor dependent mechanism. However, potential contributions of purinergic signaling in the RTN to cardiorespiratory function in conscious animals have not been tested. METHODS Cardiorespiratory activity of unrestrained awake rats were measured in response to RTN injections of ATP, and during exposure to hypercapnia (7% CO2) or hypoxia (8% O2) under control conditions and after bilateral RTN injections of P2 receptor blockers (PPADS or MRS2179). RESULTS Unilateral injection of ATP into the RTN increased cardiorespiratory output by a P2-recepor dependent mechanism. We also show that bilateral RTN injections of a non-specific P2 receptor blocker (pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate (PPADS) reduced the ventilatory response to hypercapnia (7% CO2) and hypoxia (8% O2) in unanesthetized rats. Conversely, bilateral injections of a specific P2Y1-receptor blocker (MRS2179) into the RTN had no measurable effect on ventilatory responses elicited by hypercapnia or hypoxia. CONCLUSION These data exclude P2Y1 receptor involvement in the chemosensory control of breathing at the level of the RTN, and show that ATP-mediated purinergic signaling contributes to central and peripheral chemoreflex control of breathing and blood pressure in awake rats.

Cardiovascular dysfunction associated with neurodegeneration in an experimental model of Parkinson’s disease

“…Pulsatile arterial pressure (PAP), mean arterial pressure (MAP) and heart rate (HR) were recorded in unanesthetized, freely moving rats as previously described (Favero et al, 2011;Takakura et al, 2014;Barna et al, 2016). Briefly, one day before the experiments, under IP injection of ketamine combined with xylazine anesthesia, polyethylene tubing (PE-10 connected to PE-50; Clay Adams, Parsippany, NJ, USA) was inserted into the femoral vein and abdominal aorta through the femoral artery.…”

Cholinergic neurons in the pedunculopontine tegmental nucleus modulate breathing in rats by direct projections to the retrotrapezoid nucleus

“…The cannula was tunnelled S.C. to the back of the rats to allow access in unrestrained, freely moving rats. This cannula was used later to measure pulsatile arterial pressure, mean arterial pressure (MAP) and heart rate (HR) in the unanaesthetized awake state, as described previously Barna et al 2016).…”

Waste

“…The lungs exchange, also in a tightly regulated manner, the metabolic product CO2 for oxygen . In addition, the organ multitasks as a homoeostatic organ: angiotensin I is converted to angiotensin II.…”