Central nervous system monoamine neurotransmitter turnover in primary and obesity-related human hypertension.

Recent experiments in laboratory animals have challenged the conventional view that the dominant effect of CNS noradrenergic neurons in cardiovascular control is sympathetic nervous inhibition and blood pressure reduction, describing instead sympathetic activation. We have tested whether such a stimulant effect on sympathetic outflow is also evident in human hypertension. CNS norepinephrine turnover was estimated from the combined overflow of norepinephrine, MHPG and DHPG into the internal jugular veins. Cerebral blood flow scans allowed differentiation between cortical and subcortical jugular venous drainage. In patients with pure autonomic failure, jugular overflow of norepinephrine and metabolites was not reduced, indicating brain neurons and not cerebrovascular sympathetics was the source. In healthy men, CNS norepinephrine turnover and muscle sympathetic nerve activity were directly related (p < 0.02). Administration of the ganglion blocker, trimethaphan, caused a compensatory five-fold increase in jugular overflow of MHPG. Conversely, intravenous clonidine reduced CNS norepinephrine turnover by approximately 50%, this possibly representing a mechanism of drug action. In cardiac failure patients, sympathetic nervous activation was associated with a trebling of CNS norepinephrine turnover (p < 0.01). In untreated patients with essential hypertension, the sympathetic activation present was associated with 250% higher CNS norepinephrine turnover (p < 0.01), but in subcortical brain regions only. A close and direct relation exists between brain norepinephrine turnover and human sympathetic nervous activity. CNS release of norepinephrine, presumably in the forebrain where noradrenergic neurons are sympathoexcitatory and pressor, mediates increased sympathetic nerve firing in patients with essential hypertension.