Topiramate treatment in Wistar rats during childhood induces sex-specific vascular dysfunction in adulthood.

Autor: Vidigal CB; Department of Physiological Sciences, State University of Londrina, Londrina, Brazil., Moura KF; Graduation Program of Physiological Sciences, Department of Physiological Sciences, State University of Londrina, Londrina, Brazil., Costa TJ; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil., Borges LI; Department of Physiological Sciences, State University of Londrina, Londrina, Brazil., Figaro PMM; Department of Histology, State University of Londrina, Londrina, Brazil., Pinto IC; Department of Pharmaceutical Sciences, State University of Londrina, Londrina, Brazil., de Andrade FG; Graduation Program of Physiological Sciences, Department of Physiological Sciences, State University of Londrina, Londrina, Brazil; Department of Histology, State University of Londrina, Londrina, Brazil., Gerardin DCC; Department of Physiological Sciences, State University of Londrina, Londrina, Brazil; Graduation Program of Physiological Sciences, Department of Physiological Sciences, State University of Londrina, Londrina, Brazil., Casagrande R; Department of Pharmaceutical Sciences, State University of Londrina, Londrina, Brazil., Tostes RC; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil., Franco MDC; Department of Physiology, Federal University of Sao Paulo, Sao Paulo, Brazil., Ceravolo GS; Department of Physiological Sciences, State University of Londrina, Londrina, Brazil; Graduation Program of Physiological Sciences, Department of Physiological Sciences, State University of Londrina, Londrina, Brazil. Electronic address: gsceravolo@uel.br.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2022 Jan 01; Vol. 288, pp. 120189. Date of Electronic Publication: 2021 Dec 01.
DOI: 10.1016/j.lfs.2021.120189
Abstrakt: The present study determined whether treatment during childhood with topiramate (TPM), a new generation antiepileptic drug, results in altered aortic reactivity in adult male and female rats. We also sought to understand the role of endothelium-derived contractile factors in TPM-induced vascular dysfunction. Male and female Wistar rats were treated with TPM (41 mg/kg/day) or water (TPM vehicle) by gavage during childhood (postnatal day, 16-28). In adulthood, thoracic aorta reactivity to phenylephrine (phenyl), as well as aortic thickness and expression of cyclooxygenases (COX-1 and COX-2), NOX2, and p47 phox were evaluated. The aortic response to phenyl was increased in male and female rats from the TPM group when compared with the control group. In TPM male rats, the hyperreactivity to phenyl was abrogated by the inhibition of NADPH oxidase and COX-2, while in female rats, responses were restored only by inhibition of COX-2. In addition, TPM male rats presented aortic hypertrophy and increased expression of NOX-2 and p47phox, while TPM female rats showed increased COX-2 aortic expression. Taken together, for the first-time, the present study provides evidence that treatment with TPM during childhood causes vascular dysfunction in adulthood, and that the mechanism underlying the vascular effects of TPM is sex-specific.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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