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Ventilatory responses to acute and chronic hypoxia in mice: effects of dopamine D 2 receptors

2000; American Physiological Society; Volume: 89; Issue: 3 Linguagem: Inglês

10.1152/jappl.2000.89.3.1142

8750-7587

Kimberly A. Huey, Malcolm J. Low, Michele A. Kelly, R. Juarez, Joseph M. Szewczak, F. L. Powell,

Sleep and Wakefulness Research

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.