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on July 1, 2002

Circulation. 2002
Published online before print July 1, 2002, doi: 10.1161/01.CIR.0000022844.50161.3B
A more recent version of this article appeared on July 23, 2002
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Right arrow Autonomic, reflex, and neurohumoral control of circulation
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Submitted on March 26, 2002
Revised on May 9, 2002
Accepted on May 9, 2002

Catechol-O-Methyltransferase and Blood Pressure in Humans

Jens Jordan MD*, Axel Lipp MD, Jens Tank MD, Christoph Schröder MD, Mandy Stoffels RN, Gabriele Franke RN, Andre Diedrich MD, Guy Arnold MD, David S. Goldstein MD, PhD, Arya M. Sharma MD, and Friedrich C. Luft MD

From Franz-Volhard Clinical Research Center and HELIOS Klinikum Berlin (J.J., J.T., C.S., M.S., G.F., A.M.S., F.C.L.) and the Department of Neurology (A.L., G.A.), Medical Faculty of the Charité, Humboldt-University, Berlin, Germany; Autonomic Dysfunction Service, Vanderbilt University, Nashville, Tenn (A.D.); and the Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md (D.S.G.).

* To whom correspondence should be addressed. E-mail: jordan{at}fvk-berlin.de.

Background—Whether catechol-O-methyltransferase (COMT), the enzyme that metabolizes extraneuronal norepinephrine, contributes to blood pressure regulation in humans is unknown.

Methods and Results—We studied incremental doses of the COMT inhibitor entacapone, the sympathetic stimulant yohimbine, and placebo in 7 patients with multiple system atrophy (Shy Drager syndrome). We selected these unique subjects because norepinephrine exerts an exaggerated increase in blood pressure in these patients. Autonomic regulation was characterized with intravenous phenylephrine, nitroprusside, and trimethaphan. Patients were extremely hypersensitive to phenylephrine and nitroprusside. Trimethaphan elicited a profound depressor response. Phenylephrine sensitivity increased only slightly during ganglionic blockade. Entacapone increased systolic blood pressure dose-dependently; however, the pressor response to yohimbine was {approx}3.5 times greater than the maximal response to entacapone.

Conclusions—COMT inhibition elicits a moderate, dose-dependent pressor response in the setting of severely impaired baroreflex buffering. Patients with multiple system atrophy allow for the characterization of subtle manipulations of norepinephrine turnover and blood pressure regulation in small numbers of subjects.
Key words: baroreflex • nervous system, autonomic • multiple system atrophy • Shy-Drager syndrome • receptors, adrenergic






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