DIFFERENTIAL CONTROL OF VENTILATION AMONG INBRED STRAINS OF MICE

The role genetic factors play in ventilatory control was examined by c hallenging eight inbred strains of mice to acute hypercapnia under nor moxic and hypoxic conditions. Age-matched mice were exposed for 3-5 mi n to inspired gases of the following composition (FICO2:FIO2) 0.03:0.1 0, 2) 0.03:0.21, 3) 0.08:0.10, and 4) 0.08:0.21, with intermittent roo m air exposures. Breathing frequency (f) and tidal volume (VT) of unan esthetized, unrestrained mice were assessed by whole body plethysmogra phy. During room air breathing, significant (P < 0.01) interstrain dif ferences were noted in the pattern, but minute ventilation (VE) did no t differ among the strains. Relative to room air, mild hypercapnia wit h hypoxia (0.03:0.10) significantly (P < 0.01) elevated VE in each str ain, and the percent increase in VE of the DBA/2J strain was significa ntly (P < 0.05) greater than the other strains. The ventilatory respon se to these conditions was achieved primarily by a significant (P < 0. 01) increase in f among the strains. During severely hypercapnic normo xia (0.08:0.21) and hypoxia (0.08:0.10), the increase in VE was signif icantly (P < 0.01) greatest in the C57BL/6J (B6) mice and least in the C3H/HeJ (C3) mice. The difference in hypercapnic VE between B6 and C3 strains was largely due to a significantly (P < 0.01) greater increas e in VT by B6 mice. On the assumption that environmental factors were identical, these data suggest that genetic determinants govern interst rain variation in the magnitude and pattern of breathing during hypoxi a and hypercapnia. Moreover, hypoxic and hypercapnic ventilatory respo nses appear to be influenced by different genetic mechanisms.