Clonidine reduces elevated cerebrospinal fluid catecholamine levels in patients with essential hypertension

Cubeddu, Luigi X.; Hoffmann, Irene; d'Avila, Joana C; Barbella, Yarisma; Ordaz, P

doi:10.1016/0024-3205(84)90393-x

Cited by 18 publications

(15 citation statements)

References 22 publications

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“…Our findings are broadly similar to those reported by Martin et al," Cubeddu et al , 18 and Bertilsson et al" However, one of these studies 17 involved normotensive amnesic subjects, while another 19 measured only catecholamine metabolites.…”

Section: Discussionsupporting

confidence: 81%

“…Cubeddu et al 18 recently found that clonidine lowered levels of NE, but not epinephrine (E) or dopamine (DA), in the CSF and plasma of hypertensive subjects, while Bertilsson et al 19 described a clonidine-induced fall in levels of the NE metabolite 4-hydroxy-3-methoxyphenylglycol, suggesting a decreased release or turnover of NE in CSF.…”

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confidence: 99%

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confidence: 99%

“…14 " 16 Martin et al, 17 however, reported that clonidine decreased NE levels and increased levels of the dopamine metabolite homovanillic acid (HVA) in the cerebrospinal fluid (CSF) of five normotensive subjects with amnesic disorders. Cubeddu et al 18 recently found that clonidine lowered levels of NE, but not epinephrine (E) or dopamine (DA), in the CSF and plasma of hypertensive subjects, while Bertilsson et al19 described a clonidine-induced fall in levels of the NE metabolite 4-hydroxy-3-methoxyphenylglycol, suggesting a decreased release or turnover of NE in CSF.Because catecholamines in plasma penetrate the blood-brain barrier poorly, 20 " 22 and brain areas rich in NE lie in close proximity to the CSF, …”

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confidence: 99%

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Effects of clonidine on central and peripheral nerve tone in primary hypertension.

Sullivan¹,

Quattro²,

Foti³

et al. 1986

Hypertension

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SUMMARY To define the mechanisms whereby clonidine lowers blood pressure, we measured cerebrospinal fluid and plasma levels of norepinephrine, normetanephrine, epinephrine, dopamine, and the dopamine metabolite homovanillic acid in 10 primary hypertensive subjects before and after 3 months of clonidine treatment (mean dose, 0.68 mg/day). Catecholamines were measured by radioenzymatic methods. Cerebrospinal fluid and plasma sampling was performed after subjects had fasted and remained supine overnight, and plasma sampling was repeated 2 hours later, after subjects had ambulated. Supine and upright blood pressure fell, as might be expected. Cerebrospinal fluid levels of norepinephrine and normetanephrine fell significantly, but dopamine and homovanillic acid levels were unchanged. Plasma norepinephrine, normetanephrine, and epinephrine levels decreased 30 to 50%, and supine dopamine levels also fell. The percent fall in supine blood pressure was related to the fall of cerebrospinal fluid and plasma norepinephrine. There were also positive relationships between the decreases of plasma norepinephrine and of normetanephrine and dopamine. The cerebrospinal fluid/plasma norepinephrine ratio was unaffected by clonidine, suggesting that the drug lowered both pools equally. Our findings indicate that clonidine decreases both central and peripheral norepinephrine activity. The dopaminergic activity of cerebrospinal fluid was unaffected by clonidine, and though plasma dopamine levels tended to be lower after treatment, mean plasma prolactin level, an index of dopaminergic activity, was also unchanged. The fall in plasma epinephrine level is probably related to diminished sympathetic adrenomeduilary stimulation and is unlikely to contribute to clonidine's antihypertensive action. These results also suggest that measurement of normetanephrine in cerebrospinal fluid and plasma provides a good index of norepinephrine activity. (Hypertension 8: 611-617, 1986) KEY WORDS * plasma catecholamines cerebrospinal fluid essential hypertension • effects of clonidine T HERE is evidence, albeit controversial, 1 that sympathetic nervous hyperactivity associated with raised circulating plasma catecholamine levels is involved in the pathogenesis of essential hypertension.2 " 4 Norepinephrine (NE) is the principal neurotransmitter of the sympathetic nervous system 5 and is formed locally in the nerve terminals from the amino acid tyrosine and dopamine. Clonidine is reported to lower blood pressure through central mechanisms Received April 17, 1985; accepted December 9, 1985. studies with clonidine relate to its effects on peripheral catecholamine levels. 14 " 16 Martin et al., 17 however, reported that clonidine decreased NE levels and increased levels of the dopamine metabolite homovanillic acid (HVA) in the cerebrospinal fluid (CSF) of five normotensive subjects with amnesic disorders. Cubeddu et al. 18 recently found that clonidine lowered levels of NE, but not epinephrine (E) or dopamine (DA), in the CSF and plasma of hypertensive su...

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Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Effects of clonidine on central and peripheral nerve tone in primary hypertension.

Sullivan¹,

Quattro²,

Foti³

et al. 1986

Hypertension

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“…However, the results of our in vivo study differ from these in vitro studies. Since epinephrine has been reported to have an additive effect on the corticotropin releasing hormone-induced ACTH release, 22 and since clonidine inhibits the centrally mediated stimulatory adrenergic influences 23 and lowers not only plasma but also cerebrospinal fluid level of catecholamines, 24 the mechanisms of inhibition of £-endorphin release may be due to clonidine-induced de- crease of corticotropin releasing hormone, which may partly explain the differences between in vivo and in vitro studies.…”

Section: Discussionmentioning

confidence: 86%

Central alpha 2-adrenergic stimulation increases neurointermediate lobe immunoreactive beta-endorphin in spontaneously hypertensive rats.

Yasunari¹,

Kanayama²,

Kohno³

et al. 1987

Hypertension

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A possible influence of the central alpha 2-adrenergic system on beta-endorphin was examined in rat anterior pituitary, neurointermediate lobe, and plasma. The concentration of beta-endorphin in anterior pituitary, neurointermediate lobe, and plasma was determined by radioimmunoassay 15 minutes after subcutaneous injection of clonidine in 14-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Clonidine reduced the concentration of the plasma beta-endorphinlike immunoreactivity in SHR and to a lesser extent in WKY. No significant changes in the concentration of beta-endorphinlike immunoreactivity were observed in anterior pituitary. Clonidine increased the concentration of neurointermediate lobe beta-endorphinlike immunoreactivity in SHR in a dose-related manner but did not affect the concentration in WKY. Administration of yohimbine (1 mg/kg) completely blocked the clonidine-induced increase of neurointermediate lobe beta-endorphinlike immunoreactivity in SHR, while prazosin (1 mg/kg) had no effect. These data suggest that the central alpha 2-adrenergic activation increases the neurointermediate lobe concentration of beta-endorphinlike immunoreactivity in SHR by suppressing beta-endorphin release from the neurointermediate lobe into the circulation.

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Effects of Alzheimer's Disease and Normal Aging on Cerebrospinal Fluid Norepinephrine Responses to Yohimbine and Clonidine

Peskind

Wingerson

Murray

et al. 1995

Arch Gen Psychiatry

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Clonidine reduces elevated cerebrospinal fluid catecholamine levels in patients with essential hypertension

Cited by 18 publications

References 22 publications

Effects of clonidine on central and peripheral nerve tone in primary hypertension.

Effects of clonidine on central and peripheral nerve tone in primary hypertension.

Central alpha 2-adrenergic stimulation increases neurointermediate lobe immunoreactive beta-endorphin in spontaneously hypertensive rats.

Effects of Alzheimer's Disease and Normal Aging on Cerebrospinal Fluid Norepinephrine Responses to Yohimbine and Clonidine

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