Intermittent hypercapnia produces long‐term changes of phrenic and renal sympathetic nerve activities that are serotonin dependent

Abstract

This study was performed to investigate long‐term changes of peak phrenic (pPNA) and renal sympathetic nerve (RSNA) activities during and following acute intermittent hypercapnic exposures. Urethane anesthetized, vagotomized, paralyzed and mechanically ventilated male Sprague‐Dawley rats, were exposed to the acute intermittent hypercapnia protocol consisting of 5 hypercapnic episodes (15% CO2). Experimental groups were pretreated with either methysergide (3 mg/kg iv, MeHC) or WAY‐100635 (3 mg/kg iv, WAY) prior to the onset of the first hypercapnia. PPNA or RSNA and blood pressure were recorded throughout the protocol and analyzed before and during hypercapnic exposures, and 15 (T15), 30 (T30) and 60 (T60) minutes after the last hypercapnic episode. PPNA did not significantly change at T15, T30 and T60 compared to baseline. In the MeHC group, pPNA significantly decreased at T30 and T60 (by 41.3 ± 5.3%; and by 46.1 ± 6.9%, P<0.005), compared to baseline values. In the WAY group, there were no significant changes in the pPNA at T15, T30, and T60 compared to baseline values. RSNA increased during hypercapnia and remained elevated at T15, T30 and T60 compared to baseline. In the WAY group RSNA increased during hypercapnia but returned to the baseline level at T60 (95.4 ± 23.1%). Acute intermittent hypercapnia induced long‐term depression of the pPNA following acute intermittent hypercapnia exposure only after blockade of serotonin receptors in anesthetized rats. On the other hand, acute intermittent hypercapnia evoked long‐term facilitation of the RSNA that was attenuated after blockade of serotonin receptors. Support: Croatian Science Foundation 09/165.