The brainstem network controlling blood pressure: an important role for pressor sites in the caudal medulla and cervical spinal cord
Although medullary control of blood pressure (BP) has been extensively studied, the contribution of critical regions, such as pressor sites in the caudal medulla and upper cervical spinal cord and the lateral tegmental field, remains controversial and underappreciated. A series of pressor sites caudal to the caudal ventrolateral medulla (CVLM), including the caudal pressor area (CPA) and medullocervical pressor area, play an important role in control of BP. Activation and inhibition of these sites elicits pressor and depressor responses, respectively. Basal sympathetic tone is provided principally by the medullary lateral tegmental field and rostral ventrolateral medulla (RVLM). RVLM presympathetic neurons, which project to and drive preganglionic sympathetic somata in the intermediolateral cell column, are powerfully regulated by neurons in CVLM via tonic and phasic inhibition. The current state of knowledge is summarized thus: rostrocaudally organized columns of pressor sites caudal to CVLM extend to the upper cervical spinal cord; CPA pressor responses are RVLM-dependent; CPA mediates pressor responses by (first) inhibiting RVLM-projecting inhibitory CVLM units and (second) activating RVLM-projecting excitatory CVLM units; the chemoreflex is CPA-dependent; the baroreflex is CPA-independent; pressor responses to raphe obscurus stimulation are CPA-dependent; and medullocervical pressor area pressor responses are RVLM-independent, likely mediated by direct projections to the intermediolateral cell column. In this review, we seek to underscore and characterize the critical role played by the caudal medulla and upper cervical spinal cord in BP regulation and highlight important gaps in knowledge in interactions between the caudal medulla and other regions controlling BP, which may prove critical in revealing central mechanisms underlying pathophysiology of, and pharmacotherapeutic targets for, hypertension.