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The hypoxic ventilatory response and TRPA 1 antagonism in conscious mice
Author(s) -
Pokorski M.,
Takeda K.,
Sato Y.,
Okada Y.
Publication year - 2014
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.12202
Subject(s) - hypoxic ventilatory response , hypercapnia , hypoxia (environmental) , antagonist , carotid body , antagonism , stimulation , blockade , ventilation (architecture) , chemistry , respiratory system , pharmacology , anesthesia , medicine , oxygen , receptor , mechanical engineering , organic chemistry , engineering
Aim Recently, TRPA 1 channels, richly expressed in both peripheral and central neural systems, have been proposed as novel sensors of changes in oxygen concentration along the hypoxic–hyperoxic continuum. In this study, we investigated the hypothesis that TRPA 1 channels blockade should profoundly affect the hypoxic ventilatory response ( HVR ). Methods We examined the chemosensory ventilatory responses in conscious mice before and after intraperitoneal administration of the specific TRPA 1 antagonist HC ‐030031 in two doses of 50 and 200 (cumulative dose 250) mg kg −1 . Ventilation and its responses to mild 13% and severe 7% hypoxia, pure O 2 , and 5% CO 2 in O 2 were recorded in a whole‐body plethysmograph. Results TRPA 1 antagonism caused a dose‐dependent attenuation of the HVR . Ventilatory stimulation was virtually abrogated in response to the mild, but it remained viable, albeit slashed, at severe hypoxia after the bigger dose of HC ‐030031. The TRPA 1 function seemed specific for the hypoxic chemoreflex as neither the response to pure O 2 nor hypercapnia was appreciably influenced by the TRPA 1 antagonist. Conclusions The study unravelled the role of TRPA 1 in shaping the ventilatory response to low‐intensity hypoxia, liable to be mediated by vagally innervated respiratory chemosensors of lower functional rank, but contradicted the TRPA 1 being indispensable for the powerful carotid body chemoreflex in face of a severe hypoxic threat.