Lowering of blood pressure during chronic suppression of central sympathetic outflow: insight from computer simulations.

1. Chronic electrical stimulation of the carotid sinuses has provided unique insight into the mechanisms that cause sustained reductions in blood pressure during chronic suppression of central sympathetic outflow. 2. Because renal denervation does not abolish the sustained fall in arterial pressure in response to baroreflex activation, this observation has seemingly challenged the concept that the kidneys play a critical role in the long-term control of arterial pressure during chronic changes in sympathetic activity. The aim of the present study was to use computer simulations to provide a more comprehensive understanding of physiological mechanisms that mediate sustained reductions in arterial pressure during prolonged baroreflex-mediated suppression of central sympathetic outflow. 3. Physiological responses to baroreflex activation under different conditions were simulated by an established mathematical model of human physiology (QHP2008; see Supporting Information (Appendix S1) provided in the online version of this article and/or http://groups.google.com/group/modelingworkshop). The model closely reproduced empirical data, providing important validation of its accuracy. 4. The simulations indicated that baroreflex-mediated suppression of renal sympathetic nerve activity does chronically increase renal excretory function but that, in addition, hormonal and haemodynamic mechanisms also contribute to this natriuretic response. The contribution of these redundant natriuretic mechanisms to the chronic lowering of blood pressure is of increased importance when suppression of renal adrenergic activity is prevented, such as after renal denervation. Activation of these redundant natriuretic mechanisms occurs at the expense of excessive fluid retention. 5. More broadly, the present study illustrates the value of numerical simulations in elucidating physiological mechanisms that are not obvious intuitively and, in some cases, not readily testable in experimental studies.