Reactive Oxygen Species within the Spinal Cord Impairs Arterial Baroreflex Control of Renal Sympathetic Nerve Activity

Clinical and experimental studies have shown that sustained increase in renal sympathetic nerve activity (rSNA) contributes to hypertension. Previous studies by our group showed that antioxidant treatments improve arterial baroreceptor reflex, which is a powerful beat-to-beat negative feedback control of arterial blood pressure (BP). We hypothesized that reactive oxygen species (ROS) contribute to arterial baroreflex control of rSNA by acting on sympathetic preganglionic neurons in the spinal cord. We then performed the intrathecal (i.t.) administration of tempol (4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-N-oxyl) (5nmol), a superoxide dismutase mimetic. We evaluated the cardiovascular effects, basal and reflex rSNA evoked by i.t. injection of tempol. No significant changes in basal levels of heart rate (HR), mean arterial pressure (MAP) and rSNA were found. However, tempol significantly increased renal reflex sympathoinhibitory responses (pre tempol: -0.61 ± 0.15; post tempol: -1.55 ± 0.14* spikes/s/mmHg). Thus, the results suggest that ROS exert a tonic inhibitory influence on the activity of spinal neurons with barosensitive properties, and it seems to be a preferential influence on fibers involved in reflex sympathoinhibitory responses. Our study raises the possibility that ROS in the spinal cord mediate part of the baroreflex dysfunction in cardiovascular diseases, such as hypertension and heart failure, which is detrimental to patient outcome.