CENTRAL-NERVOUS-SYSTEM NORADRENERGIC CONTROL OF SYMPATHETIC OUTFLOW IN NORMOTENSIVE AND HYPERTENSIVE HUMANS

We applied transmitter washout methodology, sampling internal jugular venous plasma via a percutaneously placed catheter, to study CNS norep inephrine release in humans and its relation to peripheral sympathetic activity. Norepinephrine overflows into the venous drainage of the br ain, as do its precursor, DOPA, and metabolites DHPG and MHPG, indicat ing that the blood-brain barrier provides an incomplete impediment to their outward flux from the brain. Pharmacological testing with two dr ugs which altered CNS norepinephrine turnover, the tricyclic antidepre ssant desipramine and the ganglionic blocker, trimethaphan, demonstrat ed a direct relation existed between CNS norepinephrine release and sy mpathetic nerve firing rates. In essential hypertension, the sympathet ic activation commonly present was associated with, and possibly cause d by increased CNS release of norepinephrine, manifested in elevated o verflow of norepinephrine, MHPG and DHPG from the brain. Bilateral jug ular sampling, coupled with a cerebral venous sinus scan to delineate the drainage pattern, demonstrated that this increased norepinephrine release was confined to subcortical forebrain regions.