Hypoxia induced tightly coupled augmented bursts in phrenic and splanchnic sympathetic nerve activity are eliminated by vagotomy and uncoupled by blockade of the paraventricular nucleus of the hypothalamus

Abstract

Previous experiments in conscious rats verified that hypoxia decreased mean arterial pressure (MAP), increased heart rate (HR) and increased frequency (F) and amplitude (amp) of diaphragm EMG (dia EMG). In addition to increased eupneic breathing, regularly spaced high amp, longer duration bursts in dia EMG were indicative of augmented breaths. In a separate group of conscious rats, hypoxia‐induced increases in integrated splanchnic sympathetic nerve activity (SSNA) included high amp bursts of SSNA at a frequency similar to that of augmented breaths (4 – 6 bursts/min). Current experiments in inactin anesthetized (100 mg/kg) male Sprague Dawley rats evaluated, in the same animal, the relationship between hypoxic responses in phrenic (Ph) nerve activity (PNA) and SSNA and the role of vagal afferent nerves (n = 6) and the hypothalamic paraventricular nucleus (PVN, n = 3) in augmented bursts. Inspired O2 concentration (nose cone) in freely breathing rats was initially 100% (Control, Con). To produce hypoxia, inspired O2 was slowly decreased while measuring arterial O2 saturation (sat; Mouse Ox foot clip) until PNA stabilized with regularly spaced augmented bursts. PNA and SSNA were recorded during 3 states: O2 sat levels of 100 ±2% (Control, con); 46 ± 2 % (Hypoxia, Hx); and 41 ± 2% (hypoxia after vagotomy, Hx‐VX), with recovery periods at 100% inspired O2 in between. During each of the 3 states, MAP was increased (i.v. phenylephrine, 5 μg/kg) equivalently (+48 ± 2; +52 ± 2; +48 ± 8 mmHg, respectively) and arterial baroreflex decreases in HR (−19 ± 3; −10 ±3; −17 ± 7 beats/min) and SSNA (−72 ± 4; −76 ± 10; −86 ± 24 %) were similar among the 3 states. Consistent with efferent and afferent denervation, VX alone increased HR (+ 21 ± 6 beats/min), SSNA (+69 ± 7 %), and PNA (+21 ± 9 %, P = 0.06), and decreased Ph F (−13 ± 4 breaths/min). Before and after VX, Hx decreased MAP (Hx, −47 ±5 mmHg; Hx‐VX, −60 ± 3mmHg ) and increased HR (Hx, +52 ±11; Hx‐VX, +30 ± 8 beats/min ); SSNA (Hx, +31 ± 10; Hx‐VX, +54 ± 11 %); PNA (P = 0.15; HxCon, +34 ± 16; HxVX, +32 ±22%); and Ph‐F (Hx, +17 ± 3; Hx‐VX, +14 ± 4). Augmented bursts were rare in the control state (100% O2). Prior to vagotomy, during Hx high amp bursts in SSNA (148 ± 12% of adjacent) coincided with high amp bursts in PNA (188 ±16% of adjacent) at a frequency of 5 ± 1/min and were eliminated by vagotomy. In 3 additional rats the PVN was first blocked with muscimol (2mM, 60 nl bilaterally) and the protocol repeated. Although high amplitude bursts in PNA were observed during Hx (~ 2/min) and were eliminated by VX, bursts in SSNA were not tightly coupled with bursts in PNA in 2 of the 3 rats with PVN muscimol injections. The tight correlation between high amplitude bursts in PNA and SSNA during hypoxia suggests CNS integration in initiating augmented responses in autonomic and respiratory efferent nerves. Vagal afferents, likely from pulmonary stretch receptors, are essential for initiating augmented discharge of the phrenic nerve during hypoxia and preliminary data suggests that integration within the PVN contributes to coupling of augmented phrenic bursts with sympathetic outflow.Support or Funding InformationNIH R01 HL98602This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.