Browsing by Subject "Sleep Apnea"
Now showing 1 - 4 of 4
- Results Per Page
- Sort Options
Item AT1A RECEPTOR KNOCKDOWN IN THE MEDIAN PREOPTIC NUCLEUS ATTENUATES THE SUSTAINED COMPONENT OF HYPERTENSION RESULTING FROM CHRONIC INTERMITTENT HYPOXIA(2013-04-12) Shell, BrentPurpose: Obstructive sleep apnea produces hypertension and increases sympathetic nerve activity during the hypoxic sleeping events as well as during the waking hours. This study examined a possible receptor contribution to the sustained component of hypertension. Methods: To model the hypoxemia experienced during sleep apnea, rodents are exposed to chronic intermittent hypoxia (CIH). The median preoptic nucleus (MnPO) is a forebrain region that contributes to this sustained increase in mean arterial pressure (MAP) from CIH. This region integrates information from forebrain circumventricular organs and projects to the paraventricular nucleus to influence sympathetic nerve activity. Our lab has previously shown that in response to CIH there is increased ΔFosB expression in the MnPO and that after a 7 day hypoxia protocol MnPO AT1a receptor mRNA is increased 7 fold whereas AT1b shows no change. In this study, we tested the hypothesis that MnPO AT1a receptors contribute to CIH hypertension using adult male Sprague Dawley rats injected with a neuron specific adenoviral vectors with either shRNA to knock down expression of AT1a receptors in the MnPO or a scrambled RNA sequence. Results: All rats showed an increase in MAP during the hypoxic light period, but rats receiving the AT1a knock down did not exhibit the sustained increase in MAP during the normoxic dark phase (P<.05). Conclusions: This data indicates that the AT1a receptors in the MnPO is necessary for the sustained component of hypertension resulting from CIH.Item INTERMITTENT INDUCED CHANGES IN GENE EXPRESSION IN THE MEDIAN PREOPTIC NUCLEUS (MNPO) OF RATS(2013-04-12) Saini, NiharikaPurpose: Our previous work indicated that changes in MnPO gene expression are necessary for the sustained increase in blood pressure produced by chronic intermittent hypoxia (CIH), an animal model of the hypoxemia associated with sleep apnea. This study tested the effects of a 7d CIH exposure on the expression of additional genes in the MnPO that could contribute to changes in the excitability of neurons in this region: Angiotensin receptor 1a (AT1a), Angiotensin receptor 1b (At1b), delta FBJ murine osteosarcoma viral oncogene homolog B (ΔFosB), transient receptor potential channel 4 (TRPC4), potassium-chloride cotransporter 2 (KCC2), and sodium-potassium-chloride cotransporter 1 (NKCC1). Methods: The brain was harvested from adult male rats anesthetized with inactin (100 mg/kg ip) after 7 d of CIH or 7 d of normoxia. Laser Capture Microdissection of MnPO was carried out from 10µ sections. MnPO samples were run through RNA purification, cDNA synthesis and PCR using S18 as the housekeeping gene. Results: PCR results revealed significant increases in the expression of TRPC4, ΔFosB, NKCC1 and AT1a in the MnPO of CIH treated rats relative to normoxic controls. KCC2 and AT1b gene expression in MnPO were not significantly affected by CIH. Conclusions: The results suggest that increased expression of TRPC4, ΔFosB, NKCC1 and especially AT1a could participate in the contribution of MnPO to the sustained hypertensive effects of CIH.Item MEDIAN PREOPTIC NUCLEUS NEURONS ACTIVATED FOLLOWING CHRONIC INTERMITTENT HYPOXIA PROJECT TO THE PARAVENTRICULAR NUCLEUS(2013-04-12) Faulk, KatelynnPurpose: Chronic Intermittent Hypoxia (CIH) is a model for the arterial hypoxemia seen in sleep apnea and is associated with hypertension and increased sympathetic tone. In rats, the MnPO demonstrates increased FosB expression following CIH. A major projection from the MnPO is to the paraventricular nucleus (PVN). This projection may serve as one possible pathway for increased sympathetic tone and sustained hypertension in CIH. The purpose of this study is to further characterize MnPO neurons transcriptionally activated by CIH and determine if they project to the PVN. Methods: Isoflurane anesthetized adult male rats were microinjected with 200nl of a retrograde tracer, flourogold, unilaterally into PVN. Rats were then exposed to CIH for 7 days through 3 minute periods of hypoxia (10% oxygen) and 3 minute periods of normoxia (21% oxygen) for 8 hours per day (0800-1600 h). Controls were not exposed to to room air. Forebrains were fixed through paraformaldehyde perfusion and later processed for immunohistochemistry. Antibodies used were goat polyclonal FosB (1:2000). The sections were imaged using an Olympus DSU confocal microscope. Results: In the MnPO, CIH exposure increased FosB positive cells (Control 7.75± l.l; CIH 25.7±4.4; P<0.05) and colocalization of FosB with flourogold positive cells (Control 0.67±0.4; CIH 7.25±1.2; P<0.05). Conclusions: These results show that MnPO neurons transcriptionally activated by CIH project to the PVN. P01 HL88052Item N-ACETYL CYSTEINE: A MODULATOR OF THE ARTERIOBAROREFLEX IN OBSTRUCTIVE SLEEP APNEA.(2013-04-12) Jouett, NoahPurpose: The CDC estimates that 18 million Americans have Obstructive Sleep Apnea (OSA). Although much is known clinically about OSA, the mechanisms which cause long term detrimental effects have not been fully elucidated. Prior research demonstrates that OSA causes a hypersympathetic state with decreased responsiveness to changes in blood pressure, i.e. decreased sensitivity of the arterial baroreflex (ABR). However, the mechanistic pathways underlying this decrease in ABR sensitivity remain to be identified. The goal of this study was to evaluate the potential role of reactive oxygen species (ROSs) in the modulation of the ABR in OSA. N-acetyl cysteine (NAC), a known free radical scavenger in the central nervous system (CNS), should diminish the depressive effects of intermittent hypoxia on ABR function. Thus, our hypothesis is that NAC will attenuate the sympathoexcitation observed after IH and, consequently, blunt the increase in HR typically observed. Methods: Positive and negative pressures were applied at the carotid sinus of 10 subjects using a malleable neck collar. Carotid baroreflex function (CBR) was assessed by comparing changes in heart rate for a given altered carotid sinus pressure. Blood pressure was non-invasively recorded using a finometer and heart rate was monitored by electrocardiography. After baseline measurements were recorded, the subjects were given a drink containing either NAC or a placebo treatment. After ingestion, the subjects were allowed to rest for 1 hour after which HR and CBR function were assessed. The subjects were then intermittent hypoxia trained (IHT) and HR and ABR function were obtained immediately, 30 min and 1 hour post IHT. Results: HR was found to increase with time under both placebo and NAC treatment conditions (two-way ANOVA, p ≥ 0.712). There were also no significant changes in CBR function as assessed by the operating or response ranges and maximum gain of the reflex. Conclusions: CBR control of HR, a measure of autonomic function, was not significantly altered in NAC treated subjects. This does not indicate an inability of NAC to modulate ABR function, but rather suggests other underlying mechanisms.