Ventilatory responses to acute and chronic hypoxia in mice: effects of dopamine D(2) receptors.
We used genetically engineered D(2) receptor-deficient [D(2)-(-/-)] and wild-type [D(2)-(+/+)] mice to test the hypothesis that dopamine D(2) receptors modulate the ventilatory response to acute hypoxia [hypoxic ventilatory response (HVR)] and hypercapnia [hypercapnic ventilatory response (HCVR)] and time-dependent changes in ventilation during chronic hypoxia. HVR was independent of gender in D(2)-(+/+) mice and significantly greater in D(2)-(-/-) than in D(2)-(+/+) female mice. HCVR was significantly greater in female D(2)-(+/+) mice than in male D(2)-(+/+) and was greater in D(2)-(-/-) male mice than in D(2)-(+/+) male mice. Exposure to hypoxia for 2-8 days was studied in male mice only. D(2)-(+/+) mice showed time-dependent increases in "baseline" ventilation (inspired PO(2) = 214 Torr) and hypoxic stimulated ventilation (inspired PO(2) = 70 Torr) after 8 days of acclimatization to hypoxia, but D(2)-(-/-) mice did not. Hence, dopamine D(2) receptors modulate the acute HVR and HCVR in mice in a gender-specific manner and contribute to time-dependent changes in ventilation and the acute HVR during acclimatization to hypoxia.
Huey
K A
KA
Department of Medicine, University of California, San Diego, La Jolla, California 92093-0623, USA. khuey@uci.edu
Low
M J
MJ
Kelly
M A
MA
Juarez
R
R
Szewczak
J M
JM
Powell
F L
FL
D000064:Acclimatization; D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000502:physiology*; D012119:Respiration; D012727:Sex Characteristics
D017448:Receptors, Dopamine D2