Physiological and Molecular Implications of Angiotensinergic Signaling in the Brainstem.

The endocrine renin-angiotensin system (RAS) is a key regulator of the autonomic nervous system and blood pressure (BP). Research over the past 5 decades has demonstrated that, in addition to this, circulating RAS tissues, including in the brain, express RAS components and have the capacity to generate and respond to angiotensin peptides. Recently, compelling new data have indicated the presence of renin expression within a discrete neuronal population in the nucleus ambiguus (NuAm), a brainstem region traditionally associated with parasympathetic control of heart rate (HR). These findings challenge conventional perspectives on brain RAS function and raise critical questions about its role in autonomic regulation. Here we provide a review of recent studies characterizing the NuAm and the adjacent C1 region of the rostral ventrolateral medulla (RVLM)-a key vasomotor center linked to sympathetic outflow. We revisit the hypothesis that the NuAm may influence BP and HR through both parasympathetic and sympathetic pathways through interactions with the RVLM. Furthermore, we highlight an emerging trend of sex-dependent differences in brain RAS activation. Finally, we emphasize the need for targeted molecular and physiological investigations to clarify the interplay between the NuAm and RVLM, their respective contributions to autonomic balance, and the potential involvement of brain RAS dysfunction in neurogenic hypertension.