Sympathetic long-term facilitation following acute intermittent hypoxia is similar in the diurnal rest versus active phase in vagal-intact rats.

Abstract

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 versus 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 ([Formula: see text] 40-55 mmHg) is greater in the mid-rest than in 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) versus 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. Furthermore, 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.NEW & NOTEWORTHY Acute intermittent hypoxia (AIH) is widely reported to elicit plasticity in sympathetic nerve activity in anesthetized, vagotomized rats. Here, we demonstrate that, in vagal-intact rats, only modest renal sympathetic nerve plasticity occurs (without change in mean arterial pressure) in response to AIH delivery in the diurnal rest or active phase. Similarity in AIH-induced renal sympathetic nerve plasticity versus time-dependent drift in sham rats highlights the need for careful experimental controls in studies of sympathetic plasticity.