What is the clinical evidence from this study?

Study design: Other. Population: Cyclosporin A-induced renal vasoconstriction. Intervention: Dexamethasone vs. Vehicle or Cyclosporin A alone. Primary outcome: Renal vasoconstriction and NOS isoform mRNA levels.

September 1, 1999

Dexamethasone increases eNOS gene expression and prevents renal vasoconstriction induced by cyclosporin

Key Result

Dexamethasone prevented cyclosporin A-induced renal vasoconstriction and restored glomerular hemodynamics, likely mediated by increased intrarenal NO generation via enhanced eNOS and iNOS expression.

Structured PICO

Does dexamethasone prevent cyclosporin A-induced renal vasoconstriction in uninephrectomized rats?

Population

Uninephrectomized rats treated for 7 days to evaluate the effect of dexamethasone on cyclosporin A-induced renal vasoconstriction.

Intervention

Dexamethasone 4 mg/kg for 7 days (with or without Cyclosporin A 30 mg/kg or L-NAME 10 mg/kg)

Comparator

Vehicle, Cyclosporin A 30 mg/kg alone, or Vehicle + L-NAME 10 mg/kg

Outcome

Glomerular hemodynamics (renal vasodilation/vasoconstriction) and NO synthase (NOS) isoform mRNA levels in renal cortex and medullasurrogate

Dexamethasone prevents cyclosporin A-induced renal vasoconstriction in a rat model, likely through increased intrarenal nitric oxide generation via enhanced eNOS and iNOS expression.

Abstract

Cyclosporin A (CsA)-induced renal vasoconstriction (RV) is attributed to an imbalance in vasoactive factors release. Dexamethasone (Dex) exerts a renal vasodilatory effect by a mechanism not yet characterized. This study evaluates whether the effect of Dex is mediated by NO and whether it prevents CsA-induced RV. Micropuncture studies were performed in six groups of uninephrectomized rats treated for 7 days with the following: vehicle (Veh); Veh + 4 mg/kg dexamethasone (Veh+Dex); 30 mg/kg CsA; CsA+Dex; vehicle + 10 mg/kg nitro-L-arginine methyl ester (Veh+L-NAME); and Veh+Dex+L-NAME. NO synthase (NOS) isoform mRNA levels were evaluated in renal cortex and medulla by semiquantitative RT-PCR analysis in the first four groups. Dex produced renal vasodilation, which was blocked by concomitant L-NAME administration, and the effect of Dex was associated with higher cortical and medullary endothelial NOS (eNOS) and cortical inducible NOS (iNOS) mRNA levels. In the CsA group, Dex prevented RV, restoring glomerular hemodynamics to control values. These changes were associated with further enhancement of eNOS and restoration of medullary iNOS and neuronal NOS (nNOS) expression. We conclude that Dex prevents CsA-induced RV, and its vasodilator effect could be mediated by increased intrarenal generation of NO, secondary to enhanced expression of eNOS and iNOS.

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