Inspiratory modulation of sympathetic activity is increased in female rats exposed to chronic intermittent hypoxia.

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FINDINGS: What is the central question of the study? There are sex differences in the respiratory network and in the regulation of arterial blood pressure. Female rats develop hypertension after chronic intermittent hypoxia (CIH). In this context, we evaluated the respiratory-related mechanism underlying the development of hypertension in CIH-exposed female rats. What is the main finding and its importance? Female rats exposed to CIH develop changes in the respiratory pattern related to inspiration and sympathetic overactivity phase locked to the inspiratory phase of the respiratory cycle, which is different from CIH-exposed male rats. These data suggest a specific respiratory mechanism for sympathetic overactivity in hypertensive CIH-exposed female rats. Chronic intermittent hypoxia (CIH) induces sympathetic overactivity and hypertension in male rats. Enhanced respiratory modulation of sympathetic activity in juvenile male rats exposed to CIH occurs in the expiratory phase of the respiratory cycle, characterizing changes in respiratory-sympathetic coupling. Different from other experimental models of hypertension, CIH induces an increase in arterial pressure in adult female rats similar to that observed in male rats. However, the mechanisms underlying the hypertensive phenotype in CIH-exposed female rats remain to be elucidated. Moreover, several lines of evidence have documented sex differences in respiratory network activity in response to hypoxia. Considering that CIH-exposed male rats present an increase in the respiratory modulation of sympathetic activity and there are sex differences in the respiratory network, we hypothesized that CIH-exposed female rats develop an increase in the respiratory modulation of sympathetic activity different from CIH-exposed male rats. In this study, we investigated sympathetic and respiratory activities in juvenile female rats exposed to CIH using an in situ working heart-brainstem preparation. The CIH-exposed female rats developed changes in the respiratory pattern and changes in the respiratory-sympathetic coupling marked by sympathetic overactivity phase locked to inspiration, which was different from male rats exposed to CIH. This study revealed a specific respiratory-related mechanism for sympathetic overactivity linked to inspiration that explains, at least in part, the hypertensive phenotype in female rats exposed to CIH.