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Chronic caffeine intake in adult rat inhibits carotid body sensitization produced by chronic sustained hypoxia but maintains intact chemoreflex output.
- Source :
-
Molecular pharmacology [Mol Pharmacol] 2012 Dec; Vol. 82 (6), pp. 1056-65. Date of Electronic Publication: 2012 Aug 28. - Publication Year :
- 2012
-
Abstract
- Sustained hypoxia produces a carotid body (CB) sensitization, known as acclimatization, which leads to an increase in carotid sinus nerve (CSN) activity and ensuing hyperventilation greater than expected from the prevailing partial pressure of oxygen. Whether sustained hypoxia is physiological (high altitude) or pathological (lung disease), acclimatization has a homeostatic implication because it tends to minimize hypoxia. Caffeine, the most commonly ingested psychoactive drug and a nonselective adenosine receptor antagonist, alters CB function and ventilatory responses when administered acutely. Our aim was to investigate the effect of chronic caffeine intake on CB function and acclimatization using four groups of rats: normoxic, caffeine-treated normoxic, chronically hypoxic (12% O₂, 15 days), and caffeine-treated chronically hypoxic rats. Caffeine was administered in drinking water (1 mg/ml). Caffeine ameliorated ventilatory responses to acute hypoxia in normoxic animals without altering the output of the CB (CSN neural activity). Caffeine-treated chronically hypoxic rats exhibited a decrease in the CSN response to acute hypoxia tests but maintained ventilation compared with chronically hypoxic animals. The findings related to CSN neural activity combined with the ventilatory responses indicate that caffeine alters central integration of the CB input to increase the gain of the chemoreflex and that caffeine abolishes CB acclimatization. The putative mechanisms involved in sensitization and its loss were investigated: expression of adenosine receptors in CB (A(2B)) was down-regulated and that in petrosal ganglion (A(2A)) was up-regulated in caffeine-treated chronically hypoxic rats; both adenosine and dopamine release from CB chemoreceptor cells was increased in chronic hypoxia and in caffeine-treated chronic hypoxia groups.
- Subjects :
- Acclimatization drug effects
Adenosine metabolism
Animals
Caffeine toxicity
Carotid Body metabolism
Carotid Sinus drug effects
Carotid Sinus innervation
Carotid Sinus metabolism
Dopamine metabolism
Down-Regulation drug effects
Ganglion Cysts metabolism
Hypercapnia metabolism
Hyperventilation metabolism
Partial Pressure
Pulmonary Ventilation drug effects
Rats
Rats, Wistar
Receptors, Purinergic P1 metabolism
Up-Regulation drug effects
Caffeine pharmacology
Carotid Body drug effects
Chemoreceptor Cells drug effects
Chemoreceptor Cells metabolism
Hypoxia metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0111
- Volume :
- 82
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 22930709
- Full Text :
- https://doi.org/10.1124/mol.112.081216