In a rat model of chronic intermittent hypoxia, inhibition of 5-HT2 receptors, NOX, or ROCK attenuated sympathetic hyperactivity and hypertension, highlighting a potential mechanistic pathway involving the paraventricular nucleus and carotid body.
Abstract Chronic intermittent hypoxia (CIH) is known to induce hypertension, but the mechanism is not well understood. We hypothesized that sensory plasticity of the carotid body (CB) and oxidative stress in the paraventricular nucleus (PVN) are involved in CIH‐induced hypertension. In this study, rats were exposed to CIH for 28 days (intermittent hypoxia of 21% O 2 for 60 s and 5% O 2 for 30 s, cyclically repeated for 8 hr/day) and then randomly grouped for intracerebroventricular injection of 5‐HT2 receptor antagonist ritanserin, Rho‐associated protein kinase (ROCK) inhibitor Y‐27632, and NADPH oxidase (NOX) inhibitor diphenyleneiodonium (DPI), respectively. We found that CIH increased blood pressure (BP), elevated carotid sinus nerve (CSN) and renal sympathetic nerve (RSN) activities, oxidative stress, and cell apoptosis in PVN. NOX‐derived reactive oxygen species (ROS) production and cell apoptosis decreased when CIH‐induced activation of 5‐HT/5‐HT2AR/PKC signaling was inhibited by ritanserin. In addition, RhoA expression was downregulated when oxidative stress was attenuated by DPI, while Y‐27632 decreased the expression of endothelin‐1, which is overexpressed in the vascular wall during hypertension. Moreover, treatment with ritanserin, DPI or Y‐27632 attenuated the sensory plasticity and sympathetic hyperactivity as well as CIH‐induced elevation of BP. In conclusion, CIH‐induced activation of 5‐HT/5‐HT2AR/PKC signaling contributes to NOX‐derived oxidative stress in PVN, which may cause sensory plasticity of CB, RSN hyperactivity, and elevated BP.
Liu et al. (Fri,) studied this question.