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

Shing, Cecilia M., Fassett, Robert G., 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: 337-346. doi:10.1111/j.1432-2277.2011.01420.x


Author Shing, Cecilia M.
Fassett, Robert G.
Brown, Lindsay
Coombes, Jeff S.
Title The effects of immunosuppressants on vascular function, systemic oxidative stress and inflammation in rats
Journal name Transplant International   Check publisher's open access policy
ISSN 0934-0874
1432-2277
Publication date 2012-03-01
Sub-type Article (original research)
DOI 10.1111/j.1432-2277.2011.01420.x
Volume 25
Issue 3
Start page 337
End page 346
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2013
Language eng
Abstract 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 ex vivo 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.
Keyword Cyclosporine A
Everolimus
F2-isoprostanes
Sirolimus
Tacrolimus
Vascular function
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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