In:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 287, No. 6 ( 2004-12), p. R1407-R1418
Abstract:
We tested the hypothesis that carbenoxolone, a pharmacological inhibitor of gap junctions, would reduce the ventilatory response to CO 2 when focally perfused within the retrotrapezoid nucleus (RTN). We tested this hypothesis by measuring minute ventilation (V E ), tidal volume (V T ), and respiratory frequency (F R ) responses to increasing concentrations of inspired CO 2 (Fi CO 2 = 0–8%) in rats during wakefulness. We confirmed that the RTN was chemosensitive by perfusing the RTN unilaterally with either acetazolamide (AZ; 10 μM) or hypercapnic artificial cerebrospinal fluid equilibrated with 50% CO 2 (pH ∼6.5). Focal perfusion of AZ or hypercapnic aCSF increased V E , V T , and F R during exposure to room air. Carbenoxolone (300 μM) focally perfused into the RTN decreased V E and V T in animals 〈 11 wk of age, but V E and V T were increased in animals 〉 12 wk of age. Glyzyrrhizic acid, a congener of carbenoxolone, did not change V E , V T , or F R when focally perfused into the RTN. Carbenoxolone binds to the mineralocorticoid receptor, but spironolactone (10 μM) did not block the disinhibition of V E or V T in older animals when combined with carbenoxolone. Thus the RTN is a CO 2 chemosensory site in all ages tested, but the function of gap junctions in the chemosensory process varies substantially among animals of different ages: gap junctions amplify the ventilatory response to CO 2 in younger animals, but appear to inhibit the ventilatory response to CO 2 in older animals.
Type of Medium:
Online Resource
ISSN:
0363-6119
,
1522-1490
DOI:
10.1152/ajpregu.00404.2004
Language:
English
Publisher:
American Physiological Society
Publication Date:
2004
detail.hit.zdb_id:
1477297-8
SSG:
12
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