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- Title:
Effect of sirolimus on renal ischaemia/reperfusion injury in normotensive and hypertensive rats.
- Document type:
- Journal Article; Article
- Author(s):
- Viklický, O; Bohmová, R; Ouyang, N; Honsová, E; Lodererová, A; Mandys, V; Vítko, S; Lutz, J; Heemann, UW
- Abstract:
- BACKGROUND: Renal ischaemia/reperfusion (I/R) injury and hypertension represent major alloantigen-independent factors contributing to the development of chronic allograft nephropathy of renal allografts. In the present study, we investigated the effect of the anti-proliferative immunosuppressant, sirolimus (SIR), in a model of accelerated renal injury in hypertensive transgenic rats (TGRs). Twenty anaesthetized uninephrectomized TGRs with renin overproduction [TGR(mREN2)27] and 20 normotensive Han SD (SD) rats as genetic controls had their renal pedicles clipped for 45 min and were subsequently treated with either SIR (0.5 mg/kg per day, orally) or placebo ( n=10 in each group) for 16 weeks, after which time the kidneys were harvested for morphological and immunohistochemical analysis. High-renin hypertension aggravated the functional and structural changes induced by I/R in SD animals: both SIR-treated and untreated TGRs exhibited significantly greater proteinuria and suffered from more severe glomerulosclerosis ( P<0.01) and vasculopathy ( P<0.01), as well as compensatory renal hypertrophy ( P<0.01) and tissue TGF-beta1 expression, than both normotensive SD groups ( P<0.01). SIR-treated SD rats showed reduced proteinuria ( P<0.01), glomerulosclerosis ( P<0.01), and TGF-beta1 expression in the glomerular epithelium and proximal tubuli ( P<0.05) compared with placebo-treated SD rats. SIR-treated TGRs had significantly lower proteinuria at week 4 after I/R ( P<0.01) than placebo-treated TGRs, but there were no significant differences thereafter. Morphological patterns were similar in treated and untreated TGRs at week 16. High-renin-induced hypertension aggravated the renal injury induced by I/R. Sirolimus treatment ameliorated some late functional and morphological changes induced by I/R injury in hypertensive TGRs but, particularly, in normotensive SD rats.
- Journal title abbreviation:
- Transpl Int
- Year:
- 2004
- Journal volume:
- 17
- Journal issue:
- 8
- Pages contribution:
- 432-41
- Language:
- eng
- Fulltext / DOI:
- doi:10.1007/s00147-004-0746-z
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/15338121
- Print-ISSN:
- 0934-0874
- TUM Institution:
- Fachgebiet Nephrologie (Prof. Heemann)
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