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Sexual dimorphism in left ventricular and electrocardiographic effects of chronic cyclosporine in rats
Author(s) -
ElMas Mahmoud M,
ElBassossy Hany M.,
Banjar Zainy M
Publication year - 2016
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.30.1_supplement.716.7
Subject(s) - medicine , blood pressure , endocrinology , cardiotoxicity , qt interval , cardiology , diastole , heart rate , isovolumic relaxation time , doppler echocardiography , toxicity
Although cardiotoxicity has been recognized as one of the adverse effects of the immunosuppressant drug cyclosporine A (CSA), limited or no information is available regarding the sex specificity of CSA cardiotoxicity. Here we tested the hypothesis that the left ventricular (LV) and electrocardiographic effects of chronic CSA and related inflammatory and histopathological derangements are sex‐related. Adult male and female rats were treated with CSA (15 mg/kg/day, sc) or its vehicle for three weeks. Afterwards, studies were undertaken to assess: (i) LV and electrocardiographic characteristics, and (ii) alterations in LV inflammatory (nuclear factor kappa B, NFκB; angiotensin receptors type 1, AT 1 ) and histopathological profiles. In both male and female rats, CSA significantly reduced LV slope of end‐systolic pressure volume relationship (ESPVR), and isovolumic relaxation constant (Tau), suggesting LV systolic and diastolic dysfunction. Histopathologically, the treatment of either rat sex with CSA resulted in vascular congestion, blood extravasation, and pyknotic or even absent nuclei. We also report sex‐dependent electrocardiographic effects for CSA. Whereas CSA increased QTc and T peak trend intervals in male rats, markers of LV arrhythmogenesis, evidence of prolonged AV conduction was noted in female rats as reflected by the prolonged P duration and PR interval. Other sex‐related effects for CSA included (i) increased blood cholesterol, rate of rise (dp/dt max ) and fall (dp/dt min ) in LV pressure and LV content of NFκB and AT 1 expression in male rats, and (ii) increased LV content of adiponectin and elevated systolic and diastolic blood pressures in female rats. Although the two rat sexes are prone to the negative LV influences of CSA, the male rat seems to be more vulnerable to inflammatory and LV adverse effects of CSA. Support or Funding Information This work was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under grant No. (166 ‐ 1001 ‐D1435). The authors, therefore, acknowledge with thanks DSR technical and financial support