Altered central catecholaminergic transmission and cardiovascular disease.

Numerous studies, some of which date back more than three decades, have established a link between disorders of the cardiovascular system and the catecholaminergic system of the brain. Central noradrenergic (and putative adrenergic) neurones are involved in numerous brain functions, and there appears to be more than one mechanism via which a dysfunction of central nor/adrenergic signalling may be detrimental to the cardiovascular system. Moreover, in some cases, such as essential hypertension, altered noradrenergic transmission could play a causative role. Numerous controversies are evident throughout the literature, which are very difficult to explain without much better understanding of the basic physiology of central noradrenergic transmission. Recently, using a combination of novel molecular, electrochemical and imaging techniques, we have started to unravel how noradrenergic neurones in the brain store and release their transmitter. Targeted long-term modulation of specific noradrenergic cell groups in defined brain areas using viral gene transfer is helping to clarify the links between central catecholamines and cardiovascular control in health and disease. These studies may reveal new therapeutic strategies for various cardiovascular diseases which are accompanied by heightened sympathetic nerve activity.