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


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 approximately 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.
Jordan
Jens
J
Franz-Volhard Clinical Research Center and HELIOS Klinikum Berlin, Medical Faculty of the Charité, Humboldt-University, Berlin, Germany. jordan@fvk-berlin.de
Lipp
Axel
A
Tank
Jens
J
Schröder
Christoph
C
Stoffels
Mandy
M
Franke
Gabriele
G
Diedrich
Andre
A
Arnold
Guy
G
Goldstein
David S
DS
Sharma
Arya M
AM
Luft
Friedrich C
FC
D017704:Baroreflex; D001794:Blood Pressure / Q000187:drug effects; D002394:Catechol O-Methyltransferase / Q000502:physiology*; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D012791:Shy-Drager Syndrome / Q000175:diagnosis / Q000201:enzymology* / Q000503:physiopathology*; D013566:Sympathomimetics / Q000494:pharmacology; D014294:Trimethaphan / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D009570:Nitriles; D013566:Sympathomimetics; D009599:Nitroprusside; D010656:Phenylephrine; D015016:Yohimbine; C071192:entacapone; D014294:Trimethaphan; D002394:Catechol O-Methyltransferase