Acute and chronic effects of carotid body denervation on ventilation and chemoreflexes in three rat strains

GC Mouradian Jr, HV Forster… - The Journal of …, 2012 - Wiley Online Library
The Journal of Physiology, 2012Wiley Online Library
Key points• Carbon dioxide (CO2) provides a major chemical stimulus to breathe, primarily
through the activity of CO2/pH sensors called chemoreceptors in the brainstem and in the
carotid body.• Carotid body denervation (CBD) causes hypoventilation at rest and reduces
ventilatory sensitivity to CO2 in multiple mammalian species, suggesting an important role of
the carotid bodies in determining levels of ventilation relative to the CO2 drive to breathe.•
CBD in three strains of adult rats with large inherent differences in CO2 sensitivity causes …
Key points
  • • 
    Carbon dioxide (CO2) provides a major chemical stimulus to breathe, primarily through the activity of CO2/pH sensors called chemoreceptors in the brainstem and in the carotid body.
  • • 
    Carotid body denervation (CBD) causes hypoventilation at rest and reduces ventilatory sensitivity to CO2 in multiple mammalian species, suggesting an important role of the carotid bodies in determining levels of ventilation relative to the CO2 drive to breathe.
  • • 
    CBD in three strains of adult rats with large inherent differences in CO2 sensitivity causes hypoventilation at rest but has no effect on CO2 sensitivity.
  • • 
    These data from rats reinforce the concept that the carotid bodies provide a tonic facilitatory drive to breathe, but differ from other species suggesting a minimal contribution of the carotid bodies to CO2 sensitivity in rats.
Abstract  Brown Norway (BN) rats have a relatively specific deficit in CO2 sensitivity. This deficit could be due to an abnormally weak carotid body contribution to CO2 sensitivity. Accordingly, we tested the hypothesis that CBD would have less of an effect on eupnoeic breathing and CO2 sensitivity in the BN rats compared to other rat strains. We measured ventilation and blood gases at rest (eupnoea) and during hypoxia (= 0.12) or hypercapnia (= 0.07) before and up to 23 days after bilateral or Sham CBD in BN, Sprague–Dawley (SD) and Dahl Salt‐Sensitive (SS) rats. In all three rat strains, CBD elicited eupnoeic hypoventilation (Δ+8.7–11.0 mmHg) 1–2 days post‐CBD (P < 0.05), and attenuated ventilatory responses to hypoxia (P < 0.05) and venous sodium cyanide (NaCN; P < 0.05), while sham CBD had no effect on resting breathing, blood gases or chemoreflexes (P > 0.05). In contrast, CBD had no effect on CO2 sensitivity (Δ/Δ) in all strains (P > 0.05). Eupnoeic returned to pre‐CBD values within 15–23 days post‐CBD. Thus, the effects of CBD in rats (1) further support an important role for the carotid bodies in eupnoeic blood gas regulation, (2) suggest that the carotid bodies are not a major determinant of CO2 sensitivity in rats, and (3) may not support the concept of an interaction among the peripheral and central chemoreceptors in rats.
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