Chronic hypoxia increases the gain of the hypoxic ventilatory response by a mechanism in the central nervous system.
We studied the effects of the ventilatory stimulant doxapram to test the hypothesis that chronic hypoxia increases the translation of carotid body afferent input into ventilatory motor efferent output by the central nervous system. Chronic hypoxia (inspired Po(2) = 70 Torr, 2 days) significantly increased the ventilatory response to an intravenous infusion of a high dose of doxapram in conscious, unrestrained rats breathing normoxic or hypoxic gas. The in vitro carotid body response to hypoxia increased with chronic hypoxia, but the response was not increased with a high dose of doxapram. Similarly, the phrenic nerve response to doxapram in anesthetized rats with carotid bodies denervated did not change with 7 days of chronic hypoxia. The results support the hypothesis that chronic hypoxia causes plasticity in the central component of the carotid chemoreceptor ventilatory reflex, which increases the hypoxic ventilatory response. We conclude that doxapram provides a promising tool to study the time course of changes in the central gain of the hypoxic ventilatory response during chronic hypoxia in awake animals and humans.
Wilkinson
Katherine A
KA
Dept. of Medicine, Univ. of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0623, USA.
Huey
Kimberly
K
Dinger
Bruce
B
He
Liang
L
Fidone
Salvatore
S
Powell
Frank L
FL
D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D002344:Carotid Body / Q000503:physiopathology; D002490:Central Nervous System / Q000187:drug effects / Q000503:physiopathology*; D002908:Chronic Disease; D003714:Denervation; D004195:Disease Models, Animal; D004315:Doxapram / Q000494:pharmacology; D004525:Efferent Pathways / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects / Q000294:innervation*; D008297:Male; D009473:Neuronal Plasticity; D010791:Phrenic Nerve / Q000503:physiopathology; D012123:Pulmonary Ventilation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D019141:Respiratory System Agents / Q000494:pharmacology; D013997:Time Factors
D019141:Respiratory System Agents; D004315:Doxapram