Chelation of iron in in vitro carotid body emulates the effects of hypoxia. The role iron plays in in vivo ventilatory responses is unclear. In the current study we addressed this issue by examining the effects of chronic iron chelation on the hypoxic ventilatory response in 9 conscious Wistar rats. Acute responses to 14 and 9% O(2)in N(2) were recorded in the same rat before and then after 7 and 14 days of continuous iron chelation. Iron chelation was carried out with ciclopirox olamine (CPX) in a dose of 20 mg/kg daily, i.p. Ventilation was recorded with whole body plethysmography. We found that the peak hypoxic ventilation (V(E) achieved during 14 and 9% hypoxia was lower by 239.6+/-55.4(SE) and 269.6.2+/-69.2 ml min(-1)kg(-1), respectively, in the rats treated with CPX for 7 days. The decreases were not intensified by a longer duration of iron chelation. CPX failed to alter hypoxic sensitivity, assessed from the gain of peak V(E) with increasing strength of the hypoxic stimulus. In conclusion, we believe we have shown that iron is operational in shaping the hypoxic ventilatory response, but is not liable to be the underlying determinant of the hypoxic chemoreflex.
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