Control of Blood Pressure Variability Across Behavioral States by Brainstem Adrenergic Neurons

Background: Short-term blood pressure (BP) variability is increasingly recognized as an independent predictor of cardiovascular and cerebrovascular risks, yet the central neural mechanisms that govern this variability, particularly across behavioral states, remain poorly defined. Methods: We investigated the role of rostral ventrolateral medulla C1 (RVLMC1) neurons in short-term BP regulation during sleep-wake transitions and physical activity in freely behaving rats. Genetically targeted fiber photometry was used to record RVLMC1 neuronal activity across behavioral states. The contribution of feedback from the arterial baroreflex to the activity of RVLMC1 neurons was assessed using sinoaortic denervation. Selective genetic ablation of RVLMC1 neurons was performed to determine their role in BP regulation. Results: RVLMC1 neurons exhibited state-dependent activity, with rapid activation during arousal from nonrapid eye movement sleep, sustained activity during rapid eye movement sleep, and further recruitment during physical activity. Baroreflex input contributed to the modulation of RVLMC1 neuron activity by pharmacological manipulations of BP and transitions from nonrapid eye movement sleep to rapid eye movement sleep. Selective ablation of RVLMC1 neurons did not alter mean BP but resulted in marked BP instability during arousal and movement. Conclusions: RVLMC1 neurons stabilize BP during changes in the behavioral state by integrating arousal-related central drive with baroreceptor feedback. Disruption of these neurons leads to increased short-term BP variability despite preserved mean BP, providing a potential neural mechanism underlying pathological BP instability.