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Isoniazid Protects Against Angiotensin II‐Induced Cardiac Hypertrophy in Sprague Dawley Rats
Author(s) -
Elkhatali Samya,
ElSherbeni Ahmed,
Elshenawy Osama,
Abdelhamid Ghada,
ElKadi Ayman
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.778.6
Subject(s) - metabolite , chemistry , endocrinology , medicine , angiotensin ii , pharmacology , microsome , renin–angiotensin system , metabolism , cardiac hypertrophy , muscle hypertrophy , isoniazid , biochemistry , enzyme , blood pressure , tuberculosis , pathology
Cytochrome P450 (CYP)‐derived Arachidonic acid (AA) metabolites are reported to exhibit potent biological activities. Isoniazid (INH) is a well‐known CYP modulator that can lead to alterations in cardiac CYP‐mediated AA metabolism. We aimed to determine the effect of INH on cardiac CYP‐mediated AA metabolism, and the biological effect of INH treatment on Angiotensin II (Ang II)‐induced cardiac hypertrophy. Male Sprague Dawley rats were treated with INH (200 mg/kg/day), Ang II (450 ng/kg/min), or both for 2 weeks. Ang II‐induced cardiac hypertrophy was assessed by heart weight to tibia length ratio and echocardiography. CYP expression was determined by real‐time PCR and Western blot. CYP‐derived AA metabolites were measured by liquid chromatography–electrospray ionization‐mass spectrometry. Echocardiographic analysis showed that INH improved heart functions in addition to reversing the increase in heart weight to tibia length ratio caused by Ang II. The cardioprotective effect of INH was associated with an increased level of cardiac 19‐HETE. In addition, INH significantly reduced the cardiotoxic AA metabolite, 20‐HETE‐induced by Ang II treatment. However, it caused a significant decrease in the cardioprotective AA metabolite, 14,15‐EET. This demonstrates that INH alters the expression of cardiac CYP and their associated AA metabolites and partially protects against Ang II‐induced cardiac hypertrophy. Our study further confirms the role of CYP, and their associated AA metabolites in cardiac hypertrophy development. This work was supported by Canadian Institutes of Health Research (CIHR) Grant to A.O.S; S.E is the recipient of the Libyan government scholarship.