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Telmisartan and captopril ameliorate pregabalin-induced heart failure in rats.

Authors
  • Awwad, Zeinab M1
  • El-Ganainy, Samar O2
  • ElMallah, Ahmed I3
  • Khattab, Mahmoud M4
  • El-Khatib, Aiman S4
  • 1 Department of Pharmacology and Therapeutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt. Electronic address: [email protected] , (Egypt)
  • 2 Department of Pharmacology and Therapeutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt. , (Egypt)
  • 3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. , (Egypt)
  • 4 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. , (Egypt)
Type
Published Article
Journal
Toxicology
Publication Date
Dec 01, 2019
Volume
428
Pages
152310–152310
Identifiers
DOI: 10.1016/j.tox.2019.152310
PMID: 31629013
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Pregabalin (PRG) is highly effective in the treatment of epilepsy, neuropathic pain and anxiety disorders. Despite its potential benefits, PRG administration has been reported to induce or exacerbate heart failure (HF). It has been previously documented that overactivation of the renin angiotensin system (RAS) is involved in HF pathophysiological mechanism. The target of the current study was to examine the possible cardioprotective effect of telmisartan (Tel), an angiotensin II type 1 receptor (AT1R) blocker, compared with that of captopril (Cap), an angiotensin converting enzyme (ACE) inhibitor, in ameliorating PRG-induced HF in rats by assessing morphometric, echocardiographic and histopathological parameters. Furthermore, to investigate the role of RAS blockade by the two drugs in guarding against PRG-induced changes in cardiac angiotensin 1-7 (Ang 1-7) and angiotensin II (Ang II) levels, in addition to myocardial expression of ACE2, ACE, Mas receptor (MasR) and AT1R. Results showed that PRG administration induced morphometric, echocardiographic and histopathological deleterious alterations and significantly elevated cardiac Ang II, ACE and AT1R levels, while reduced Ang 1-7, ACE2 and MasR cardiac levels. Concurrent treatment with either Tel or Cap reversed PRG-induced morphometric, echocardiographic and histopathological abnormalities and revealed prominent protection against PRG-induced HF via downregulation of ACE/Ang II/AT1R and upregulation of ACE2/Ang 1-7/MasR axes. These are the first findings to demonstrate that the potential benefits of Tel and Cap are mediated by counteracting the altered balance between the RAS axes induced by PRG. Hence; Tel and Cap may attenuate PRG-induced HF partially through stimulation of ACE2/Ang 1-7/MasR pathway. Copyright © 2019 Elsevier B.V. All rights reserved.

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