Core Viewpoint - The research published by Stephen Liberles' team at Harvard Medical School reveals the role of vagal blood volume receptors in compensating for hemorrhage and posture changes, highlighting the importance of PIEZO2 protein-expressing sensory neurons in maintaining blood pressure stability during sudden changes in body position or blood loss [3][4]. Group 1: Mechanism of Vagal Nerve - The vagus nerve connects the brain to internal organs, reporting on bodily states and maintaining circulatory stability through the perception of blood pressure, blood oxygen, and chemical changes [5]. - Previous studies identified baroreceptors for blood pressure monitoring, but the function of cardiac mechanoreceptors remained unclear due to the closed-loop nature of the cardiovascular system [5]. - The research team utilized genetic tools to manipulate specific neurons in mice, discovering PIEZO2-expressing sensory neurons in the vagus nerve that respond to blood volume changes [5][6]. Group 2: Experimental Findings - In tilt table tests simulating orthostatic hypotension, normal mice experienced a temporary drop in blood pressure upon standing but quickly compensated through increased heart rate. In contrast, mice lacking PIEZO2 genes showed persistent hypotension and failed to compensate [7]. - The vagus nerve's activity was found to synchronize with heartbeats, with two peaks of electrical activity corresponding to atrial and ventricular contractions, reflecting blood volume changes [9]. - During simulated traumatic blood loss, normal mice maintained blood pressure despite losing 20%-25% of blood volume, while PIEZO2 knockout mice experienced rapid decompensation and significantly lower survival rates [11]. Group 3: Clinical Implications - This research addresses a long-standing question in physiology and has significant clinical implications, suggesting that dysfunction in volume receptors can lead to symptoms like dizziness and fainting during standing [14]. - The findings may provide new therapeutic targets for conditions such as neurogenic orthostatic hypotension and post-traumatic circulatory failure, potentially leading to drug interventions aimed at these neural pathways [14].