Respiratory modulation of sympathetic activity is attenuated in adult rats conditioned with chronic hypobaric hypoxia

•Chronic hypobaric hypoxia attenuates respiratory modulation of sympathetic activity.•Respiratory modulation of sympathetic activity is inconsistent from breath-to-breath.•Respiratory and sympathetic motor activities do not express their dynamics during and after hypoxia.•Repetitive acute hypoxic exposures does not restore the hypoxic response, evoke long-term facilitation and enhance the respiratory-modulation of sympathetic activity.

Respiratory modulation of sympathetic nerve activity (SNA) depends on numerous factors including prior experience. In our studies, exposing naïve adult, male Sprague-Dawley rats to acute intermittent hypoxia (AIH) enhanced respiratory-modulation of splanchnic SNA (sSNA); whereas conditioning them to chronic hypobaric hypoxia (CHH) attenuated modulation. Further, AIH can evoke increased SNA in the absence phrenic long-term facilitation. We hypothesized that AIH would restore respiratory modulation of SNA in CHH rats. In anesthetized, CHH-conditioned (0.5 atm, 2 wks) rats (n = 16), we recorded phrenic and sSNA before during and after AIH (8% O2 for 45s every 5 min for 1 h). At baseline, sSNA was not modulated with respiration. The sSNA was not recruited during a single brief exposure of hypoxia nor after 10 repetitive exposures. Further, the sSNA chemoresponse was not restored 1 h after completing AIH. Thus, CHH-conditioning blocked the short-term plasticity expressed in sympatho-respiratory efferent activities and this was associated with reduced respiratory modulation of sympathetic activity and with attenuation of the sympatho-respiratory chemoresponse.