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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Contribution of oxidative stress and prostanoids in endothelial dysfunction induced by chronic fluoxetine treatment

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Author(s):
Simplicio, Janaina A. [1, 2] ; Resstel, Leonardo B. [3] ; Tirapelli, Daniela P. C. [4] ; D'Orleans-Juste, Pedro [5] ; Tirapelli, Carlos R. [2]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Programa Posgrad Farmacol, BR-14040902 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Escola Enfermagem Ribeirao Preto, Farmacol Lab, Dept Enfermagem Psiquiat & Ciencias Humanas, Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Farmacol, Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cirurgia & Anat, Ribeirao Preto, SP - Brazil
[5] Univ Sherbrooke, Dept Pharmacol, Sherbrooke, PQ - Canada
Total Affiliations: 5
Document type: Journal article
Source: VASCULAR PHARMACOLOGY; v. 73, p. 124-137, OCT 2015.
Web of Science Citations: 12
Abstract

Objectives: The effects of chronic fluoxetine treatment were investigated on blood pressure and on vascular reactivity in the isolated rat aorta. Methods and results: Male Wistar rats were treated with fluoxetine (10 mg/kg/day) for 21 days. Fluoxetine increased systolic blood pressure. Chronic, but not acute, fluoxetine treatment increased the contractile response induced by phenylephrine, serotonin (5-HT) and KCl in endothelium-intact rat aortas. L-NAME and ODQ did not alter the contraction induced by phenylephrine and 5-HT in aortic rings from fluoxetine-treated rats. Tiron, SC-560 and AH6809 reversed the increase in the contractile response to phenylephrine and 5-HT in aortas from fluoxetine-treated rats. Fluoxetine treatment increased superoxide anion generation (O-2(-)) and the expression of cyclooxygenase (COX)-1 in the rat aorta. Reduced expression of nNOS, but not eNOS or iNOS was observed in animals treated with fluoxetine. Fluoxetine treatment increased prostaglandin (PG)F-2 alpha levels but did not affect thromboxane (TX)B-2 levels in the rat aorta. Reduced hydrogen peroxide (H2O2) levels and increased catalase (CAT) activity were observed after treatment. Conclusions: The major new finding of our study is that chronic fluoxetine treatment induces endothelial dysfunction, which alters vascular responsiveness by a mechanism that involves increased oxidative stress and the generation of a COX-derived vasoconstrictor prostanoid (PGF(2 alpha)). Moreover, our results evidenced a relation between the period of treatment with fluoxetine and the magnitude in the increment of blood pressure. Finally, our findings raise the possibility that fluoxetine treatment increases the risk for vascular injury, a response that could predisposes to cardiovascular diseases. (C) 2015 Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 10/05815-4 - Assessment of the role of angiotensin II in the cardiovascular effects induced by acute ethanol consumption
Grantee:Carlos Renato Tirapelli
Support Opportunities: Regular Research Grants
FAPESP's process: 13/00808-8 - Consequences of ethanol withdrawal on the vasculature and the systemic and local renin-angiotensin system (ras)
Grantee:Carlos Renato Tirapelli
Support Opportunities: Regular Research Grants