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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Time-dependent modulation of carotid body afferent activity during and after intermittent hypoxia

Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada

Submitted 22 November 2004 ; accepted in final form 21 January 2005

The ventilatory response to several minutes of hypoxia consists of various time-dependent phenomena, some of which occur during hypoxia (e.g., short-term depression), whereas others appear on return to normoxia (e.g., posthypoxic frequency decline). Additional phenomena can be elicited by acute, intermittent hypoxia (e.g., progressive augmentation, long-term facilitation). Current data suggest that these phenomena originate centrally. We tested the hypothesis that carotid body afferent activity undergoes time-dependent modulation, consistent with a direct role in these ventilatory phenomena. Using an in vitro rat carotid body preparation, we found that 1) afferent activity declined during the first 5 min of severe (40 Torr PO₂), moderate (60 Torr PO₂), or mild (80 Torr PO₂) hypoxia; 2) after return to normoxia (100 Torr PO₂) and after several minutes of moderate or severe hypoxia, afferent activity was transiently reduced compared with prehypoxic levels; and 3) with successive 5-min bouts of mild, moderate, or severe hypoxia, afferent activity during bouts increased progressively. We call these phenomena sensory hypoxic decline, sensory posthypoxic decline, and sensory progressive augmentation, respectively. These phenomena were stimulus specific: similar phenomena were not seen with 5-min bouts of normoxic hypercapnia (100 Torr PO₂ and 50–60 Torr PCO₂) or hypoxic hypocapnia (60 Torr PO₂ and 30 Torr PCO₂). However, bouts of either normoxic hypercapnia or hypocapnic hypoxia resulted in sensory long-term facilitation. We suggest time-dependent carotid body activity acts in parallel with central mechanisms to shape the dynamics of ventilatory responses to respiratory chemostimuli.

control of breathing; blood gases; peripheral chemoreceptor; response; dynamics

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