Revealing the Mysterious Mechanism of Acute Baroreceptor Resetting

Arterial baroreceptors acutely reset to lower pressure and strain sensitivity when arterial blood pressure (BP) increases for a few seconds to minutes, allowing precise control of instantaneous BP fluctuations. However, despite extensive research, the underlying mechanism remains debated and elusive. Three mechanisms have been proposed: (1) changes in the viscoelastic properties of the vessel wall, potentially reducing strain on the sensors, (2) shifts in membrane ionic levels that may hyperpolarize the sensors, and (3) modulation of sensitivity by endothelial substances. Although plausible, each mechanism remains questionable. Recently, a multiple-sensor theory (MST) has been proposed to characterize airway sensory units, suggesting that a single mechanosensory unit houses multiple heterogeneous types of sensors. According to MST, the sensor with the highest discharge rate serves as the pacemaker, setting the unit’s discharge frequency. This theory explains previously unexplainable phenomena in the airway sensory system. In the present study, we aim to determine whether MST applies to baroreceptor units and can explain acute resetting by demonstrating a pacemaker-switching mechanism within the units. By definition, a pacemaker switch or sensor deactivation within a unit constitutes resetting, wherein unit activity diminishes even as BP remains elevated. We examined single-unit activity in the aortic depressor nerve of anesthetized rabbits in response to intravenous bolus injections of phenylephrine (10 mM, 0.2 ml). Baroreceptor unit activity progressively increased with rising BP; however, in 46% of units examined, activity abruptly ceased or decreased in a stepwise fashion to a lower level after BP reached a plateau around 200 mmHg for one to two minutes. Additionally, following deactivation, sensors could be reactivated by lowering BP through blood withdrawal and deactivated again by raising BP with blood reinfusion. These electrophysiological data demonstrate that over-excitation, either pharmacologically or by increasing blood volume, deactivates the pacemaker sensors, switching the unit discharge to a new pacemaker with a lower frequency. This resets the baroreceptor unit behavior. Our findings support previous morphological evidence that multiple heterogeneous sensors share an afferent axon, thus reinforcing MST. Establishing MST represents a significant advancement in the field, necessitating data reinterpretation and a redefinition of mechanosensors, sensory units, and their reflex functions. It opens a new research frontier to explore how different sensors interact to encode information and how the central nervous system decodes this information to generate reflex responses. Supported by a VA Merit Review Award (PULM-024-17S) This abstract was presented at the American Physiology Summit 2025 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.