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Purinergic receptor blockade in the retrotrapezoid nucleus attenuates the respiratory chemoreflexes in awake rats
Author(s) -
Barna B. F.,
Takakura A. C.,
Mulkey D. K.,
Moreira T. S.
Publication year - 2016
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12637
Subject(s) - ppads , purinergic receptor , chemoreceptor , central chemoreceptors , hypercapnia , peripheral chemoreceptors , purinergic signalling , rostral ventrolateral medulla , endocrinology , p2 receptor , medicine , hypoxic ventilatory response , cardiorespiratory fitness , neuroscience , chemistry , adenosine , receptor , respiratory system , adenosine receptor , medulla oblongata , central nervous system , biology , agonist
Aim Recent evidence suggests that adenosine triphosfate ( ATP )‐mediated purinergic signalling at the level of the rostral ventrolateral medulla contributes to both central and peripheral chemoreceptor control of breathing and blood pressure: neurones in the retrotrapezoid nucleus ( RTN ) function as central chemoreceptors in part by responding to CO 2 ‐evoked ATP release by activation of yet unknown P2 receptors, and nearby catecholaminergic C1 neurones regulate blood pressure responses to peripheral chemoreceptor activation by a P2Y1 receptor‐dependent mechanism. However, potential contributions of purinergic signalling in the RTN to cardiorespiratory function in conscious animals have not been tested. Methods Cardiorespiratory activity of unrestrained awake rats was measured in response to RTN injections of ATP , and during exposure to hypercapnia (7% CO 2 ) or hypoxia (8% O 2 ) under control conditions and after bilateral RTN injections of P2 receptor blockers ( PPADS or MRS 2179). 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% CO 2 ) and hypoxia (8% O 2 ) in unanesthetized rats. Conversely, bilateral injections of a specific P2Y1 receptor blocker ( MRS 2179) 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 signalling contributes to central and peripheral chemoreflex control of breathing and blood pressure in awake rats.