INTERNAL JUGULAR VENOUS SPILLOVER OF NORADRENALINE AND METABOLITES AND THEIR ASSOCIATION WITH SYMPATHETIC NERVOUS ACTIVITY

It is recognized that the brain plays a pivotal role in the maintenanc e of blood pressure and the control of myocardial function. By combini ng direct sampling of internal jugular venous blood with a noradrenali ne isotope dilution method, for examining neuronal transmitter release , and microneurographic nerve recording, we were able to quantify the release of central nervous system noradrenaline and its metabolites an d investigate their association with efferent sympathetic nervous outf low in healthy subjects and patients with pure autonomic failure. To f urther investigate the relationship between brain noradrenaline, sympa thetic nervous activity and blood pressure regulation we examined brai n catecholamine turnover, based on the internal jugular venous overflo w of noradrenaline and its principal central nervous system metabolite s, in response to a variety of pharmacological challenges. A substanti al increase was seen in brain noradrenaline turnover following trimeth aphan, presumably resulting from a compensatory response in sympathoex citatory forebrain noradrenergic neurones in the face of interruption of sympathetic neural traffic and reduction in arterial blood pressure , in contrast, reduction in central nervous system noradrenaline turno ver accompanied the blood pressure fall produced by intravenous clonid ine administration, thus representing the blood pressure lowering acti on of the drug. Following vasodilatation elicited by intravenous adren aline infusion, brain noradrenaline turnover increased in parallel wit h elevation in muscle sympathetic nervous activity. While it is diffic ult to assess the source oi the noradrenaline and metabolites determin ed in our studies, available evidence implicates noradrenergic cell gr oups of the posterolateral hypothalamus, amygdala, the A5 region and t he locus coeruleus as being involved in the regulation of sympathetic outflow and autonomic cardiovascular control.