Regulation of the caudal ventrolateral medulla by glutamatergic and respiratory-related inputs.

摘要

Many prevalent human conditions, including chronic pulmonary disease, sleep apnea, and obesity, are characterized by concomitant changes in respiratory and cardiovascular function. Mounting evidence suggests the hypertension that presents in many of these patients is attributable to a chronic elevation in sympathetic nerve activity to the vasculature that may be related to changes in central respiratory drive. The neural network that regulates central respiratory drive provides a significant input to the neural network that promotes sympathetic vasomotor tone, as evident by respiratory-related activity in peripheral sympathetic nerves. Changes in central respiratory drive are known to cause changes in arterial pressure via changes in sympathetic nerve activity, but the neural circuitry that connects these systems is not known. We hypothesized that neurons within the caudal ventrolateral medulla (CVLM), in addition to their well established role conferring homeostatic changes in sympathetic nerve activity during acute changes in arterial pressure, have an underappreciated role in the promotion of respiratory-related activity in the sympathetic nerves that control cardiovascular function. The principal findings from specific aims designed to investigate this hypothesis are: (1) glutamatergic inputs to the CVLM are enhanced under conditions of elevated central respiratory drive, (2) CVLM neurons have distinct patterns of respiratory modulated activity that are not dependent upon cardiovascular-related inputs, (3) CVLM neurons respond to hypoxia in a way that may support hypoxia-induced, respiratory-related changes in sympathetic nerve activity, and (4) glutamatergic and GABAergic inputs to the CVLM, most likely of respiratory origin, modulate the magnitude of the sympathetic response to hypoxia. These data are the first to implicate the CVLM as a primary site for cardio-respiratory integration and further suggest these neurons participate in the complex physiological responses to acute hypoxia.;Index words. sympathetic nerve activity, medulla, arterial pressure, respiration