Premium
Ibuprofen does not reverse time‐dependent increase in hypoxic ventilation in chronically hypoxic rats
Author(s) -
De La Zerda David J,
Go Ariel,
Ries Andrew,
Soler Xavier,
Powell Frank L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.721.5
Subject(s) - hypoxic ventilatory response , hypoxia (environmental) , carotid body , endocrinology , medicine , respiratory system , saline , plethysmograph , chemoreceptor , anesthesia , ventilation (architecture) , respiration , chemistry , receptor , oxygen , carotid arteries , anatomy , mechanical engineering , organic chemistry , engineering
Chronic sustained hypoxia (CSH) increases inflammatory cytokine gene expression in carotid bodies and medullary respiratory centers, and increases carotid body chemoreceptor and ventilatory responses to hypoxia in rats. Non‐steroidal anti‐inflammatory drugs (ibuprofen IBU) block these responses ( Respir.Physiol.Neurobiol. (2011) 178: 362–369 & 381–386). We tested the hypothesis that IBU can reverse these responses after they are already established in CSH. We measured cytokine expression in medullary respiratory centers and ventilatory responses in adult male rats acclimatized to CSH (P i O 2 = 70 Torr, 1 wk) before and after IBU (4 mg/kg intraperitoneal for 3 days) or sham (0.6 ml saline IP for, 3 days) treatments. We measured the effects of IBU vs. sham in normoxic animals too. Expression of mRNA for IL‐1β, IL‐6, and TNFα measured with RT‐PCR in dorsal brainstem biopsies tended to be lower with IBU compared to sham: IBU = 68, 67 and 85% of sham levels for IL‐1β, IL‐6, and TNFα, respectively. However, ventilatory and metabolic responses to hypoxia measured with barometric pressure plethysmography and stop‐flow respirometry were not significantly different between IBU and sham in CSH or normoxic rats (p>;0.1). Hence, inflammatory cytokines in the CNS and carotid bodies appear necessary for the induction but not the maintenance of an increased hypoxic ventilatory response with CSH. Supported by NIH RO1 HL‐081823.