Ventilatory responses to acute and chronic hypoxia in mice:: effects of dopamine D2 receptors

We used genetically engineered D-2 receptor-deficient [D-2-(-/-)] and wild-type [D2-(+/+)] 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 D2-(+/+) and was greater in D-2-(-/-) male mice than in D2-(+/+) 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.