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

Abstract

We used genetically engineered D2 receptor-deficient [D2-(−/−)] and wild-type [D2-(+/+)] mice to test the hypothesis that dopamine D2 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 D2-(+/+) mice and significantly greater in D2-(−/−) than in D2-(+/+) female mice. HCVR was significantly greater in female D2–(+/+) mice than in male D2-(+/+) and was greater in D2-(−/−) male mice than in D2-(+/+) male mice. Exposure to hypoxia for 2–8 days was studied in male mice only. D2-(+/+) 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 D2-(−/−) mice did not. Hence, dopamine D2receptors 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.