Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe IschemiaReperfusion Injury

Abstract EN

Background.

Nitric oxide (NO)-signal transduction plays an important role in renal ischemia/reperfusion (I/R) injury.

NO produced by endothelial NO-synthase (eNOS) has protective functions whereas NO from inducible NO-synthase (iNOS) induces impairment.

Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor (PPAR)-γ agonist exerted beneficial effects after renal I/R injury, so we investigated whether this might be causally linked with NOS imbalance.

Methods.

RGZ (5 mg/kg) was administered i.p.

to SD-rats (f) subjected to bilateral renal ischemia (60 min).

Following 24 h of reperfusion, inulin- and PAH-clearance as well as PAH-net secretion were determined.

Morphological alterations were graded by histopathological scoring.

Plasma NOx-production was measured.

eNOS and iNOS expression was analyzed by qPCR.

Cleaved caspase 3 (CC3) was determined as an apoptosis indicator and ED1 as a marker of macrophage infiltration in renal tissue.

Results.

RGZ improves renal function after renal I/R injury (PAH-/inulin-clearance, PAH-net secretion) and reduces histomorphological injury.

Additionally, RGZ reduces NOx plasma levels, ED-1 positive cell infiltration and CC3 expression.

iNOS-mRNA is reduced whereas eNOS-mRNA is increased by RGZ.

Conclusion.

RGZ has protective properties after severe renal I/R injury.

Alterations of the NO pathway regarding eNOS and iNOS could be an explanation of the underlying mechanism of RGZ protection in renal I/R injury.