Sympathetic overactivity coupled with active expiration in rats submitted to chronic intermittent hypoxia

It is well known that the respiration modulates sympathetic outflow in basal conditions. Recordings of sympathetic nerve activity demonstrated that central respiratory activity produces rhythmical oscillations in sympathetic discharge that appear mainly during inspiratory phase. This led us to hypothesize that changes in the mechanisms regulating the central entrainment between respiratory and sympathetic activities may contribute to sympathetic overactivity and hypertension. This issue was addressed using rats submitted to chronic intermittent hypoxia (CIH), in which we evaluated whether or not the sympathetic overactivity and hypertension observed in these animals were linked to changes in respiratory pattern. We verified that under baseline conditions, CIH rats exhibited a reduction in post-inspiratory activity of vagus nerve and an enhanced late-expiratory activity in abdominal motor nerve. As a consequence of this altered expiratory pattern, we observed that CIH rats showed an additional burst in sympathetic activity phase-locked with the enhanced late-E expiratory activity. These findings pointed out that the entrainment between pontine-medullary expiratory and sympathetic neurons of CIH rats is strengthened, indicating for the first time in this experimental model that changes in the coupling of respiratory and sympathetic activities may contribute to hypertension. Subsequent studies performed in other models of hypertension also demonstrated similar changes, supporting the concept that alterations in central mechanisms of respiratory–sympathetic coupling is a novel and important mechanism to be considered in the pathogenesis of hypertension.