Central sympathetic overactivity: maladies and mechanisms

Abstract

There is growing evidence to suggest that many disease states are accompanied by chronic elevations in sympathetic nerve activity. The present review will specifically focus on central sympathetic overactivity and highlight three main areas of interest: 1) the pathological consequences of excessive sympathetic nerve activity; 2) the potential role of centrally derived nitric oxide in the genesis of neural dysregulation in disease; and 3) the promise of several novel therapeutic strategies targeting central sympathetic overactivity. The findings from both animal and human studies will be discussed and integrated in an attempt to provide a concise update on current work and ideas in these important areas.

Figure 1

General schematic identifying potential central neural sites involved in the regulation of sympathetic outflow. See text for details. CVO, circumventricular organs; PVN, paraventricular nucleus; NTS, nucleus tractus solitarus; CVLM, caudal ventrolateral medulla; RVLM, rostral ventrolateral medulla; IML, intermediolateral cell column.

Figure 2

Kaplan-Meier analysis of the cumulative rates of survival in patients with heart failure stratified in two groups on the basis of resting muscle SNA (MSNA, bursts/min). Rates of survival were significantly poorer in patients with resting muscle SNA values above the median value of 49 bursts/min. From Barretto et al., (2008), with permission.

Figure 3

Summary data showing the mean arterial pressure, heart rate, and renal SNA responses to intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME) in arterial baroreceptor intact rats (left panel) and baroreceptor denervated rats (right panel). In baroreceptor intact rats, systemic L-NAME evoked an initial baroreflex-mediated reduction in renal SNA that returned to baseline at 120 minutes of infusion. In contrast, a marked and sustained increase in renal SNA was found in baroreceptor-denervated rats. *P<0.05 vs. baseline; † P<0.05 vs. baroreceptor intact. Values are means ± SE. From Augustyniak et al., (2006), with permission.

Figure 4

Individual and mean data showing changes in muscle sympathetic nerve activity (Muscle SNA; bursts/100 heart beats), mean blood pressure (BP) and heart rate (HR) in 5 heart failure patients before and after one month of Simvastatin (40 mg/day). Muscle SNA was significantly reduced following statin therapy, whereas mean BP was slightly decreased and HR was largely unchanged. * represents P<0.05 vs. Pre-Simvastatin; † represents P=0.08 vs. Pre-Simvastatin. Values are means ± SE.