Direct assessment of organ specific sympathetic nervous system activity in normal and cardiovascular disease states.

The sympathetic nervous system is critical for the regulation of arterial pressure and has been implicated in contributing to the development of cardiovascular disease. Procedures for recording sympathetic tone directly were developed in humans in the 1960s and in laboratory animals in the 1970s, promising new advances in our understanding of the role of sympathetic nerve activity in health and disease. Despite these improvements, this has proven difficult for several reasons. First and foremost, chronic recordings are difficult to maintain for prolonged periods, because they require close and stable contact between the electrode and the nerve. In laboratory animals, this must be stable enough to prevent movement artifact in behaving animals. Second, there is considerable variability between individuals in resting tone and sympathetic responsiveness. This makes population comparisons particularly difficult and necessitates long-term recording in individual animals ideally. Third, the interpretation of multi-unit activity is complex, because most sympathetic nerves contain axon populations with various functions and firing characteristics. While these recordings would be more interpretable if performed on individual axons, this technology is not yet available in conscious animals. Finally, there are considerable differences between response characteristics in individual nerves, presumably because of the nature of the efferent axons contained in different nerves. The following papers were presented at a symposium entitled Direct Assessment of Organ Specific Sympathetic Nervous System Activity in Normal and Cardiovascular Disease States held on 19th of April during the Experimental Biology 2009 meeting in New Orleans, LA, USA. This symposium was designed to address these issues, particularly the differences in responsiveness between different sympathetic nerves. Recently, several laboratories have demonstrated the ability to record sympathetic tone for prolonged periods in individual animals. This technology allows one to study complex behaviours and the development of cardiovascular disease in multiple sympathetic nerves simultaneously. This approach resolves many of the problems and allows us to interpret the role of the sympathetic nervous system in single animals and in discrete organs (Guild et al. 2005). This symposium was designed to highlight the application of these techniques to improve our understanding of the role of the sympathetic nervous system in both normal cardiovascular regulation and during the development of hypertension and heart failure. Guild et al. (2010) introduce important issues that should be considered when recording sympathetic nerve activity in conscious animals. These include the quantification of results in both amplitude and frequency modes. They propose rational analyses that could provide the needed tools for standardization of nerve recordings thereby improving our ability to compare results between laboratories and species. Miki & Yoshimoto (2010) describe the importance of understanding differences in sympathetic activation during the fear-evoked freezing reaction in rats. A loud noise evokes a freezing behaviour that is associated with skeletal muscle vasodilatation and visceral vasoconstriction. This response is characterized by an increase in renal sympathetic nerve activity without a change in lumbar sympathetic tone. This, they argue, is a distinct pattern that is an adaptive response representing the ‘fight or flight’ response, with visceral vasoconstriction without a reduction in skeletal muscle blood flow. May et al. (2010) studied the responses to intracerebral sodium administration that result in increased cardiac sympathetic tone and reduced renal sympathetic tone in conscious sheep. This adaptive response enhances cardiac output and renal clearance of fluid (sodium). They also examined the effects of heart failure on burst frequency in cardiac and renal sympathetic nerves. In normal sheep, the burst frequency was considerably greater in renal compared with cardiac nerves. In contrast, pacing-induced heart failure resulted in similar, elevated burst frequencies in both nerves and the loss of volume responsiveness of the cardiac nerves. These observations reflect physiological responses and pathological alterations that are known to occur in heart failure. Osborn & Fink (2010) examined another pathological state, angiotensin-induced hypertension exacerbated by high salt intake. Angiotensin II infusion with high-salt diet increases whole body noradrenaline spillover despite a reduction in renal sympathetic nerve activity. Moreover, they present evidence that enhanced splanchnic nerve activity is critical for the development of this model of hypertension but skeletal muscle blood flow, as reflected in lumbar sympathetic tone, is largely unchanged. This ‘sympathetic signature’ suggests that discrete, organ-specific alterations in sympathetic tone are responsible for angiotensin–salt hypertension. Finally, Yemane et al. (2010) compared the sympathetic and non-sympathetic factors responsible for deoxycorticosterone acetate–salt hypertension. This model of experimental hypertension combines a mineralocorticoid excess with a high-salt intake and compromised renal function (unilateral nephrectomy) to impair the ability to reduce sodium and volume load. The model is dependent on both sympathetic and humoral factors that change during the development of hypertension. These observations suggest that the contribution of the sympathetic nervous system cannot be judged by recording from single nerves. The capability to record multi-unit activity from several sympathetic nerves will be necessary in future studies to improve our understanding of the patterns of sympathetic activation in normal and diseased states. Moreover, the ability to record sympathetic activity for 24 h will also improve our understanding of the role of the sympathetic nervous system, particularly in cardiovascular pathologies. These advances in long-term, chronic recording will provide important new information to resolve long-standing controversies regarding the role of the sympathetic nervous system in the development of cardiovascular disease.