Mechanism of Hydrocortisone Potentiation of Responses to Epinephrine and Norepinephrine in Rabbit Aorta

Hydrocortisone potentiated responses of rabbit aortic strips to catecholamines (epinephrine, norepinephrine, nordefrin, isoproterenol) but not to amines lacking the catechol nucleus (phenylephrine, synephrine, methoxamine). Contractions in response to epinephrine were increased much more than those...

Full description

Saved in:
Bibliographic Details
Published in:Circulation research 1969-03, Vol.24 (3), p.383-395
Main Author: Kalsner, Stanley
Format: Article
Language:English
Subjects:
Animals
Aorta, Thoracic - drug effects
Aorta, Thoracic - enzymology
Cocaine - pharmacology
Drug Synergism
Epinephrine - pharmacology
Hydrocortisone - pharmacology
Muscle Contraction - drug effects
Muscle, Smooth - drug effects
Muscle, Smooth - enzymology
Norepinephrine - pharmacology
Pyrogallol - pharmacology
Rabbits
Reserpine - pharmacology
Sympathomimetics - pharmacology
Transferases - antagonists & inhibitors
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Hydrocortisone potentiated responses of rabbit aortic strips to catecholamines (epinephrine, norepinephrine, nordefrin, isoproterenol) but not to amines lacking the catechol nucleus (phenylephrine, synephrine, methoxamine). Contractions in response to epinephrine were increased much more than those to norepinephrine. Neither the presence of cocaine nor pretreatment of the rabbits with reserpine impaired the potentiating action of hydrocortisone. Experiments with the oil immersion technique (to prevent loss of amine by diffusion from the tissue) demonstrated that hydrocortisone reduced the rate at which aortic strips inactivated epinephrine, apparently by inhibiting catechol-O-methyl transferase (COMT). Known inhibitors of COMT (U-0521, tropolone, pyrogallol) potentiated responses of aortic strips to epinephrine much more than to norepinephrine and also enhanced responses to isoproterenol and nordefrin to the same extent as did hydrocortisone. Known inhibitors of COMT consistently abolished the enhancing effects of hydrocortisone without materially interfering with potentiation produced by cocaine which is mediated through an independent mechanism unrelated to amine inactivation. Hydrocortisone also abolished the enhancing effects of known COMT inhibitors. It is concluded that hydrocortisone enhances the responses of vascular smooth muscle to epinephrine and norepinephrine by inhibiting a major enzymatic pathway for the inactivation of these amines.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.res.24.3.383