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Leptin Facilitates Phrenic and Abdominal Nerve Activity During Chemoreflex Activation

Leptin acts in the central nervous system (CNS) enhancing chemorespiratory responses by mechanisms not yet completely understood. In the present study, we evaluated the pulmonary ventilation and the activity of the phrenic and abdominal nerves during activation of chemoreflex in rats treated chronically with leptin. Juvenile Holtzman rats (22–28 day old) received leptin (40 mg/day/7 days) or saline infusion subcutaneously. On the 6th day of infusion, pulmonary ventilation was recorded by whole body plethysmography and on the seventh day, nerve activity was recorded in the in situ heart‐brainstem preparation. The chemoreflex response was activated by KCN (0.04%) or hypercapnia (10% CO2). In both preparations, ventilation or nerve activities were recorded before and during chemoreflex activation. Leptin reduced the gain of body weight (30 ± 9 g vs. saline: 49 ± 2 g, p <0.05). Ventilation increased more during hypercapnia in rats treated with leptin infusion (1284 ± 109 ml.kg−1.min−1, vs. saline: 967 ± 66 ml.kg−1.min−1, p <0.05). In the in situ preparation, the increased activity of the phrenic and abdominal nerve produced by the activation of chemoreflex with KCN was strongly potentiated by leptin (45% ± 9 and 263 ± 83% vs. saline: 17 ± 3% and 93 ± 45% respectively, p <0.05). Similar increased responses were observed during hypercapnia in the in situ preparation. The results suggest that leptin enhances the chemoreflex response increasing inspiratory and expiratory activities.