Acute intermittent hypoxia (AIH) and continuous hypoxia increase augmented breaths and efferent splanchnic sympathetic nerve activity in conscious rats

Abstract

Previously we reported an intensity dependent effect of continuous hypoxia to increase minute ventilation and augmented breaths (high amplitude spikes in plethysmography traces). Lesion of catecholaminergic neurons projecting to the PVN attenuated ventilatory responses to hypoxia, suggesting an important role for the PVN. Recent immunohistochemistry experiments revealed that pre‐sympathetic neurons in the PVN were activated by acute intermittent hypoxia (AIH, 5 bouts, 3 min 10% O2, separated by 5 min of 21% O2) but not by continuous 10% or 8% O2 (2 hr). Current experiments in chronically instrumented conscious rats evaluated the functional effects of continuous 8% O2 (2 hr, n = 5) and AIH (n = 5) on mean arterial pressure (MAP), heart rate (HR) and integrated efferent splanchnic sympathetic nerve activity (int. SSNA). Effects of AIH on diaphragm EMG were determined in a separate group of rats (n=9). Continuous 8% O2: Qualitatively similar to previous data using 10% O2, 2 hr continuous 8% O2 resulted in a sustained decrease in MAP (baseline = 112 ±3; 2 hr 8% O2 = 86 ± 2 mmHg) and an initial increase in HR from baseline (334 ± 6 beats/min) to 424 ± 26 beats/min at 5 min. Within 5 min of exposure to 8% O2, int SSNA increased (+258 ±22%) and remained elevated at 2 hrs (+179±92%). MAP, HR, and int SSNA returned towards control levels within 10 min after return to normoxia (21% O2). Acute Intermittent Hypoxia: MAP, HR, and diaphragm EMG were measured in 9 conscious rats previously instrumented with telemetry probes. AIH bouts increased MAP (e.g. AIH5= +7±1 mmHg), HR (e.g. AIH5= +83±8 beats/min), integrated diaphragm EMG amplitude (e.g. AIH5= +25±7%), and frequency of regular breathing (e.g. AIH5= +49±7 breaths/min). Similar to responses with continuous hypoxia, regularly spaced augmented breaths (high amplitude diaphragm EMG) were evident during bouts of AIH (e.g. AIH5= 3±1/min). In a separate group of chronically instrumented conscious rats (n =5), MAP, HR and SSNA were monitored during the AIH protocol. Similar to telemetry data, bouts of hypoxia increased MAP (e.g. AIH5= +8±2 mmHg) and HR (e.g. AIH5= +75±7 beats/min). In addition SSNA increased during hypoxic bouts (e.g. AIH5= +183±38 % from baseline). Interestingly, it appears that regularly spaced large bursts in SSNA occurred at a frequency (e.g. AIH5 =3±0/min) similar to the frequency of high amplitude bursts that were observed in diaphragm EMG in telemetry experiments. Combined with immunohistochemistry findings, we conclude that activation of pre‐sympathetic neurons in the PVN could possibly contribute directly to the increased SSNA during AIH, but activation of SSNA during continuous hypoxia (8% O2) appears to be mediated by pathways distinct from the PVN.Support or Funding InformationFunded by NIH HL 98602.