Sympathetic Long-Term Facilitation Following Acute Intermittent Hypoxia Is Similar in the Diurnal Rest vs Active Phase in Vagal-Intact Rats

Acute intermittent hypoxia (AIH) elicits long-lasting increases in phrenic and sympathetic nerve activity, effects known as phrenic (pLTF) and sympathetic long-term facilitation (sympLTF), respectively. In anesthetized, paralyzed, vagotomized and ventilated rats, pLTF magnitude following AIH consisting of 15, 1-min isocapnic hypoxic episodes ( i.e., 15x1) is greater during the mid-rest vs mid-active phase of the diurnal cycle. However, it is unknown if sympLTF exhibits similar diurnal regulation. In urethane-anesthetized, mechanically-ventilated, male Sprague-Dawley rats we hypothesized that sympLTF elicited by 15x1 AIH (PaO 2 40–55 mmHg) is greater in the mid-rest vs mid-active diurnal phase. We report renal sympathetic nerve activity (RSNA) remained elevated 90 min post-AIH, with similar responses in mid-rest ( n=20) vs mid-active phase rats ( n=17). No significant increase was observed in time control rats in either mid-rest ( n=10) or mid-active phase ( n=9). Mean ΔRSNA (%) was 142±184 during mid-rest AIH and 101±124 during mid-active AIH, versus 34±28 and 28±52 in corresponding mid-rest and mid-active time controls. There was a significant main effect of AIH on ΔRSNA (%) ( P=0.020), with no effect of time of day ( P=0.544) and no interaction ( P=0.644). Increases in RSNA following AIH were driven primarily by increases in burst amplitude and duration, with minimal changes in burst frequency. Further, mean arterial pressure did not change from baseline in any group (all P > 0.05). These findings demonstrate that AIH elicits modest increases in RSNA that are not accompanied by increases in arterial pressure and are not modulated by time-of-day, contrasting with the diurnal regulation of pLTF.