LAUSR

Interactions between hypoxic and hypercapnic signaling pathways, expressed as ventilatory changes occurring during and following a simultaneous hypoxic-hypercapnic gas challenge (HH-C) have not been determined systematically in mice. This study in unanesthetized male C57BL6 mice addressed the hypothesis that hypoxic (HX) and hypercapnic (HC) signaling events display an array of interactions indicative of co-ordination by peripheral and central respiratory mechanisms. We evaluated the ventilatory responses elicited by hypoxic (HX-C, 10%, O2, 90% N2), hypercapnic (HC-C, 5% CO2, 21%, O2, 90% N2) and HH-C (10% O2, 5%, CO2, 85% N2) challenges to determine whether ventilatory responses elicited by HH-C challenge were simply additive of responses elicited by HX-C and HC-C, or whether other patterns of interactions existed. Responses elicited by HH-C were additive for tidal volume, minute ventilation and expiratory time, among others. Responses elicited by HH-C were hypo-additive of the HX-C and HC-C responses (i.e., HH-C responses were less than expected by simple addition of HX-C and HC-C responses) for frequency of breathing, inspiratory time and relaxation time, among others. Additionally, end expiratory pause increased during HX-C, but decreased during HC-C, and HH-C, therefore showing that HC-C responses influenced the HX-C responses when given simultaneously. Return to room-air responses were additive for tidal volume and minute ventilation, among others, whereas they were hypo-additive for frequency of breathing, inspiratory time, peak inspiratory flow, apneic pause, inspiratory and expiratory drives and rejection index. These data show that HX-C and HH-C signaling pathways interact with one another in additive and often hypo-additive processes.