Proceedings of The Physiological Society

University College Cork (2004) J Physiol 560P, PC9

Communications

THE HYPOXIC AFFERENT RESPONSE OF THE RAT CAROTID BODY RESEMBLES TIME-DEPENDENT HYPOXIC VENTILATORY PHENOMENA

Cummings,Kevin J; Wilson,Richard JA;

1. Physiology and Biophysics, University of Calgary, Calgary, AB, Canada.


Exposure to acute hypoxia elicits a ventilatory response that is subject to various time-dependent phenomena, some of which occur during hypoxia (eg. hypoxic ventilatory decline) while others appear upon return to normoxia (eg. post-hypoxic frequency decline). In addition, memory components to the response exist, associated with repeated, acute hypoxic exposures (eg. progressive augmentation). Although central mechanisms, either downstream of afferent peripheral chemoreceptor input or through the direct effects of hypoxia on the brainstem, are sufficient to elicit these phenomena, little is known about the possible contribution of mechanisms arising from the carotid body. To investigate this further, we used an arterially perfused, en bloc rat carotid body preparation. Male rats (150-250g) were deeply anaesthetized in halothane (2 ml kg-1 within a 4 l chamber) until respiration ceased and animals failed to respond to a noxious paw pinch. Animals were then transected below the diaphragm, and the carotid bifurcation was immediately canulated and perfused with chilled, normoxic, normocapnic saline. After dissection, the preparation was continually perfused with warmed, normoxic, normocapnic saline in a recording chamber, with perfusion pressures close to the mean arterial pressure of the rat. The carotid sinus nerve was exposed and activity recorded with a suction electrode. We found that, during hypoxia, afferent activity from the peripheral chemoreceptors resembles these phenomena. Specifically, we found that: (a) Afferent activity declines during 5 minutes of severe (40 Torr PO2) moderate (60 Torr PO2)or mild (80 Torr PO2) hypoxia. (b) Upon returning to normoxia (100 Torr PO2) after 5 minutes of moderate or severe hypoxia, afferent activity transiently falls below that which preceded the bout. (c) Overall afferent responses progressively increase between successive 5 minute bouts of mild, moderate or severe hypoxia. We call these phenomena, sensory hypoxic decline (sHD), sensory post hypoxic decline (sPHD) and progressive augmentation (sPA), respectively. As similar responses were not observed during hypercapnic exposures, these phenomena are dependent on hypoxia per se, and not on general carotid body stimulation. Interestingly, the phenomena are prevented by hypocapnia (30 Torr PCO2) applied concurrently with moderate hypoxia, and hypocapnic hypoxia as well as normoxic hypercapnia both produce sensory long-term facilitation (sLTF). Thus, our data demonstrate novel hypoxia-specific responses of the rat carotid bodies. We suggest that time-dependent carotid body activity acts in parallel with central mechanism(s), to shape the dynamics of the hypoxic ventilatory response.

Where applicable, experiments conform with Society ethical requirements