The effects of immunosuppressants on vascular function, systemic oxidative stress and inflammation in rats

Shing, Cecilia M. and Fassett, Robert G. and Brown, Lindsay and Coombes, Jeff S. (2012) The effects of immunosuppressants on vascular function, systemic oxidative stress and inflammation in rats. Transplant International, 25 (3). pp. 337-346. ISSN 0934-0874


Immunosuppressants have been associated with increased cardiovascular disease risk. We determined the effects of calcineurin and mammalian target of rapamycin (mTOR) inhibitor administration on endothelial dysfunction and
associated inflammation and oxidative stress in adult rats. Cyclosporine A (low and high dose), sirolimus, tacrolimus, everolimus and placebo were administered to 8-week-old male Wistar rats for 10 consecutive days. Aortic vascular
endothelial and smooth muscle function were assessed exvivo in organ baths. Maximal aortic contraction to noradrenaline in sirolimus-treated rats was significantly greater than cyclosporine groups, everolimus and placebo, whereas
endothelial-dependent relaxation was significantly impaired with cyclosporine and tacrolimus compared with everolimus. Endothelial-independent relaxation was impaired in tacrolimus-treated rats compared with low dose cyclosporine,
everolimus and sirolimus. Sirolimus was associated with a reduction in plasma interleukin (IL)-1b and tumour necrosis factor (TNF)-a and higher levels of catalase and total antioxidant status. In nontransplanted rats, vascular dysfunction was evident following administration of cyclosporine A, sirolimus and tacrolimus, whereas everolimus did not compromise aortic endothelial or smooth muscle function. At the doses administered in this model, the immunosuppressants exerted varying effects on vascular function.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Copyright 2012 The Authors
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 23 Sep 2012 06:17
Last Modified: 10 Jul 2014 01:18
Uncontrolled Keywords: cyclosporine A; everolimus; F2-isoprostanes; sirolimus; tacrolimus; vascular function
Fields of Research : 11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl. Cardiovascular Diseases)
11 Medical and Health Sciences > 1107 Immunology > 110708 Transplantation Immunology
10 Technology > 1004 Medical Biotechnology > 100499 Medical Biotechnology not elsewhere classified
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Identification Number or DOI: 10.1111/j.1432-2277.2011.01420.x

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