Chronic intermittent hypoxia (CIH), a key characteristic of obstructive sleep apnea (OSA), results in a sustained increase in sympathetic activation and persistent daytime hypertension. The median preoptic nucleus (MnPO) is a crucial region in the forebrain that plays a significant role in CIH-induced hypertension. While MnPO neurons projecting to the hypothalamic paraventricular nucleus (PVN) express nitric oxide synthase (NOS), it is unclear whether NOS contributes to changes in the excitation of MnPO neurons associated with CIH. This study investigated whether NOS activity modulates the excitability of PVN-projecting MnPO neurons following CIH exposure. We hypothesize that NOS contributes to the excitability of PVN-projecting MnPO neurons in CIH. Adult male Sprague–Dawley rats received bilateral PVN injections of a retrograde AAV expressing tdTomato to label MnPO neurons projecting to the PVN. After viral expression, rats were exposed to 7 days of CIH or maintained in normoxia (NORM). Loose patch-clamp recordings were performed in acute MnPO slices to assess spontaneous firing frequency in tdTomato-labeled and unlabeled neurons. The effect of NOS inhibition was tested using bath application of the non-selective NOS inhibitor Nω-nitro-L-arginine (L-NNA; 100 μM). Two-way repeated measures ANOVA showed an overall effect of CIH to increase basal firing rate but no impact of NOS inhibition on the activity of MnPO neurons (NORM: 1.43 ± 0.19 Hz, n = 11 neurons; CIH: 3.47 ± 0.44 Hz, n =10 neurons, P = 0.05). Acute NOS inhibition with L-NNA bath application did not alter firing rates of unlabeled and labeled MnPO neurons in either NORM or CIH condition, and repeated L-NNA applications yielded no cumulative effects (P< 0.05). NOS activity does not appear to contribute to the increased excitation of PVN-projecting MnPO neurons following CIH exposure. These findings suggest that other excitatory mechanisms or alternative neuromodulatory pathways may contribute to increased MnPO activity following CIH exposure. Future studies are needed to explore the contribution of NOS to CIH and the impact of sex on NOS activity and MnPO excitability. This work is supported by NIH grant R01 HL155977. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Appiah et al. (Fri,) studied this question.