2019-08-222019-08-222015-032015-03-05https://hdl.handle.net/20.500.12503/26411Sleep apnea is associated with a sustained increase in diurnal blood pressure. Chronic Intermittent Hypoxia (CIH), which simulates the arterial hypoxemia of sleep apnea, also produces a sustained increase in diurnal blood pressure. Several CNS regions that contribute to CIH hypertension have been identified including the MnPO and paraventicular nucleus (PVN). We have shown that viral-mediated shRNA knockdown of ACE1 within MnPO selectively decreases CIH hypertension during normoxia. Our hypothesis is that ACE1 knockdown in the MnPO will decrease FosB, a neuronal activation marker, positive neurons in the PVN which is a downstream target of the MnPO. We tested this hypothesis using a viral vector containing shRNA to ACE1 within the MnPO. Isoflurane anesthetized adult male rats were microinjected in the MnPO with 500nl of an adeno-associated virus containing GFP and either shRNA against ACE1 (shACE1) or scrambled shRNA (shSCM). Mean arterial blood pressure was recorded using radio telemetry. Rats were then exposed to 7 days of CIH (3 minute periods of hypoxia (10% oxygen) and 3 minute periods of normoxia (21% oxygen) for 8 hours/day) or normoxia (room air). Immunohistochemistry was used to assess FosB stained neurons within the MnPO and PVN. FosB positive neurons increased in the MnPO and PVN following CIH in both shSCM and shACE1 groups. However, shACE1 significantly decreased the FosB positive neurons in both MnPO and PVN following CIH. The shACE1 had no effects on FosB staining in normoxic controls. These results suggest that FosB activation within the MnPO and the PVN following CIH is at least partially dependent on MnPO ACE1.enposter