title: Monoaminergic neuronal activity in subcortical brain regions in essential hypertension.
abstract: In this study we aimed to elucidate the role of central noradrenergic, dopaminergic, adrenergic and serotonergic neuronal systems in the development of essential hypertension. Fifteen untreated essential hypertensive subjects (aged 44 +/- 3 years) and 32 healthy volunteers (aged 38 +/- 3 years) participated in this study. By combining direct blood sampling techniques with cerebral blood flow scans we were able to differentiate between cortical and subcortical venous drainage of the brain. Veno-arterial MHPG, HVA and 5-HIAA plasma concentration gradients combined with internal jugular vein plasma flows were used, according to the Fick Principle, to derive metabolite spillovers which in turn were used as indicators of central noradrenergic, dopaminergic and serotonergic neuronal activity, respectively. These amine systems, in both the brainstem and forebrain, have been implicated in the regulation of sympathetic outflow and blood pressure. Total body noradrenaline spillover to plasma was concurrently measured to assess the relationship between central monoamine turnover and sympathetic activity. Compared to their healthy counterparts the hypertensive subjects had an elevated release of MHPG from subcortical brain regions (1.4 +/- 0.3 v 0.5 +/- 0.2 nmol/min, p < 0.05). An inverse relationship between blood pressure and subcortical HVA overflow existed, with the HVA overflow being significantly lower in the hypertensives (0.5 +/- 0.2 v 2.1 +/- 0.5 nmol/min, p < 0.05). Subcortical 5-HUAA overflow did not differ between the two groups, and adrenaline spillover from the brain was not detected in either group. Subcortical MHPG overflow was significantly correlated with total body NA spillover to plasma (p < 0.05). These results indicate that reciprocal aberrations in subcortical noradrenaline and dopamine turnover exist in essential hypertension. Although the physiological significance of this remains to be unequivocally elucidated we postulate that elevated subcortical noradrenergic activity, presumably in the forebrain where noradrenergic neurons are pressor, may cause sympathoexcitation and play a role in the development of essential hypertension.
authors.affiliation: Human Autonomic Function Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
authors.forename: G W
authors.initials: GW
authors.lastname: Lambert
authors.forename: C
authors.initials: C
authors.lastname: Ferrier
authors.forename: D M
authors.initials: DM
authors.lastname: Kaye
authors.forename: V
authors.initials: V
authors.lastname: Kalff
authors.forename: M J
authors.initials: MJ
authors.lastname: Kelly
authors.forename: H S
authors.initials: HS
authors.lastname: Cox
authors.forename: A G
authors.initials: AG
authors.lastname: Turner
authors.forename: G L
authors.initials: GL
authors.lastname: Jennings
authors.forename: M D
authors.initials: MD
authors.lastname: Esler
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000328:Adult; D015306:Biogenic Monoamines / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002560:Cerebrovascular Circulation; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007601:Jugular Veins; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D012016:Reference Values
chemical_list: D015306:Biogenic Monoamines; D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid