Nitric oxide and sympathetic nerve activity in the control of blood pressure.

1. Endothelial dysfunction marked by impairment in the release of nitric oxide (NO) is seen very early in the development of hypertension and is considered important in mediating the impaired vascular tone evident in essential hypertensive patients. 2. Recently, a hypothesis has emerged that NO acting as a neurotransmitter in the brain can modulate levels of sympathetic nerve activity and thereby blood pressure. The NO inhibition model of hypertension has been used to explore the possibility that a decrease in levels of NO can cause an increase in levels of sympathetic nerve activity that can mediate the hypertension. 3. In the present review, we examine the literature regarding the role of NO in setting the mean level of sympathetic nerve activity and blood pressure. Although the acute effects of NO inhibition are well understood, the chronic interaction between the sympathetic nervous system and NO has only been investigated using indirect measures of sympathetic nerve activity, such as ganglionic blockade. This has led to inconsistent results regarding the role of NO in modulating sympathetic nerve activity chronically. 4. Some of the conflicting results may be explained by differences in the 'background' levels of angiotensin (Ang) II. Evidence suggests that NO may interact with AngII and baroreceptor afferent inputs in the central nervous system to set the mean level of sympathetic nerve activity. 5. We suggest chronic NO inhibition can increase sympathetic nerve activity if baroreceptor input is intact and AngII levels are elevated. Although studies exploring the actions of NO or AngII in isolation are useful for gathering initial information, future studies should focus on their interactions and their role in setting the long-term levels of sympathetic activity and blood pressure.