Chronic intermittent hypoxia increases blood pressure and expression of FosB/ΔFosB in central autonomic regions

Knight WD, Little JT, Carreno FR, Toney GM, Mifflin SW, Cunningham JT. Chronic intermittent hypoxia increases blood pressure and expression of FosB/Delta FosB in central autonomic regions. Am J Physiol Regul Integr Comp Physiol 301: R131-R139, 2011. First published May 4, 2011; doi:10.1152/ajpregu.00830.2010.-Chronic intermittent hypoxia (CIH) models repetitive bouts of arterial hypoxemia that occur in humans suffering from obstructive sleep apnea. CIH has been linked to persistent activation of arterial chemoreceptors and the renin-angiotensin system, which have been linked to chronic elevations of sympathetic nerve activity (SNA) and mean arterial pressure (MAP). Because Fos and FosB are transcription factors involved in activator protein (AP)-1 driven central nervous system neuronal adaptations, this study determined if CIH causes increased Fos or FosB staining in brain regions that regulate SNA and autonomic function. Male Sprague Dawley rats were instrumented with telemetry transmitters for continuous recording of MAP and heart rate (HR). Rats were exposed to continuous normoxia (CON) or to CIH for 8 h/day for 7 days. CIH increased MAP by 7-10 mmHg without persistently affecting HR. A separate group of rats was killed 1 day after 7 days of CIH for immunohistochemistry. CIH did not increase Fos staining in any brain region examined. Staining for FosB/Delta FosB was increased in the organum vasculosum of the lamina terminalis (CON: 9 +/- 1; CIH: 34 +/- 3 cells/section), subfornical organ (CON: 7 +/- 2; CIH: 31 +/- 3), median preoptic nucleus (CON 15 +/- 1; CIH: 38 +/- 3), nucleus of the solitary tract (CON: 9 +/- 2; CIH: 28 +/- 4), A5 (CON: 3 +/- 1; CIH: 10 +/- 1), and rostral ventrolateral medulla (CON: 5 +/- 1; CIH: 17 +/- 2). In the paraventricular nucleus, FosB/Delta FosB staining was located mainly in the dorsal and medial parvocellular subnuclei. CIH did not increase FosB/Delta FosB staining in caudal ventrolateral medulla or supraoptic nucleus. These data indicate that CIH induces an increase in FosB/Delta FosB in autonomic nuclei and suggest that AP-1 transcriptional regulation may contribute to stable adaptive changes that support chronically elevated SNA.