EFFECTS OF AMITRIPTYLINE, FLUOXETINE, TRANYLCYPROMINE AND VENLAFAXINE ON RAT VASCULAR SMOOTH MUSCLE IN VITRO - THE ROLE OF THE ENDOTHELIUM | Health & Environmental Research Online (HERO)

HERO ID

1564655

Reference Type

Journal Article

Title

EFFECTS OF AMITRIPTYLINE, FLUOXETINE, TRANYLCYPROMINE AND VENLAFAXINE ON RAT VASCULAR SMOOTH MUSCLE IN VITRO - THE ROLE OF THE ENDOTHELIUM

Author(s)

Ribback, S; Pavlovic, D; Herbst, D; Nedeljkov-Jancic, R; Wendt, M; Nedeljkov, V; Bleich, S; Frieling, H

Year

2012

Is Peer Reviewed?

Yes

Journal

Journal of Physiology and Pharmacology
ISSN: 0867-5910
EISSN: 1899-1505

Volume

63

Issue

2

Page Numbers

119-125

PMID

22653897

Web of Science Id

WOS:000305670000002

Abstract

Hypotension is a frequent side effect of the antidepressant
treatment. It is controversial whether this effect is attributable to interactions within the
central nervous or the cardiovascular system. We examined often used antidepressants for their
vasoactive properties in vitro in rat aortal rings with and without endothelium. The influence of
pre-incubation with the antidepressants (0.5 mu M) on adrenergic elicited smooth muscle
contraction and the effects of cumulative concentrations (0.05 mu M-500 mu M) of the
antidepressants on isometric tension were measured. In addition, conceivable modulation of the
NO-cGMP, adrenergic and potassium channel pathways were examined. Amitriptyline and fluoxetine
inhibited, whereas tranylcypromine enhanced adrenergic elicited responses of smooth muscle
contraction. The antidepressants amitriptyline, fluoxetine and tranylcypromine showed, to a
different extent, vasorelaxing properties in the preparations pre-contracted with phenylephrine
0.1 mu M; the pEC50, (means and S.E.M.) in descending order of potency: amitriptyline 6.98
(0.13), fluoxetine 6.11 (0.05), tranylcypromine 5.33 (0.05) (n=8 each, preparations with
endothelium); or after pre-contraction with KCl 20 mM: fluoxetine 6.00 (0.06), tranylcypromine
4.99 (0.30), amitriptyline, 4.89 (0.11), (n=7 each, preparations with endothelium). Venlafaxine
did not relax the aortal rings and even lead to further contraction of the endothelium intact
preparations. The observed effects were partially endothelium dependent via activation of the
NO-cGMP pathway and some probably mediated through K channel activation. Amitriptyline,
fluoxetine and tranylcypromine relax rat aorta in vitro. They partially delay vascular smooth
muscle reactions to adrenergic agonists and can lead to sustained hypotension episodes despite
administration of sympathomimetic drugs.

Keywords

antidepressants; endothelium; potassium channels; relaxation; smooth muscle contraction; nitric oxide