Obstructive Sleep Apnea An Essential Role for FosB in the Median Preoptic Nucleus in the Sustained Hypertensive Effects of Chronic Intermittent Hypoxia

One of the main clinical features of obstructive sleep apnea is sustained hypertension and elevated sympathetic activity during waking hours. Chronic intermittent hypoxia (CIH), animal model of the hypoxemia associated with obstructive sleep apnea, produces a similar sustained increase in blood pressure. This study determined the role of FosB in the median preoptic nucleus (MnPO) in the sustained increase in mean arterial pressure associated with CIH. Rats were injected in the MnPO with viral vectors that expressed green fluorescent protein alone or green fluorescent protein plus a dominant-negative construct that inhibits the transcriptional effects of FosB. In green fluorescent protein–injected rats and uninjected controls, 7-day exposure to CIH increased mean arterial pressure by 7 to 10 mm Hg during both intermittent hypoxia exposure and normoxia. Dominant-negative inhibition of MnPO FosB did not affect changes in mean arterial pressure during intermittent hypoxia exposure but significantly reduced the sustained component of the blood pressure response to CIH during the normoxic dark phase. Inhibition of MnPO FosB reduced the FosB/ FosB staining in the paraventricular nucleus and rostral ventrolateral medulla but not the nucleus of the solitary tract. PCR array analysis identified 6 activator protein 1–regulated genes expressed in the MnPO that were increased by CIH exposure, ace, ace2, nos1, nos3, prdx2, and map3k3. Dominant-negative inhibition of FosB in the MnPO blocked increased expression of each of these genes in rats exposed to CIH except for Prdx2. FosB may mediate transcriptional activity in MnPO necessary for sustained CIH hypertension, suggesting that neural adaptations may contribute to diurnal hypertension in obstructive sleep apnea. (Hypertension. 2012;60:179-187.) ● Online Data Supplement