Dexamethasone increases eNOS gene expression and prevents renal vasoconstriction induced by cyclosporin.
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.
Bobadilla
N A
NA
Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, National University of Mexico, Mexico City CP 14080, Mexico. nbobadillas@mailer.main.conacyt.mx
Tapia
E
E
Jiménez
F
F
Sánchez-Lozada
L G
LG
Santamaría
J
J
Monjardín
A
A
Bolio
A
A
Gamba
G
G
Herrera-Acosta
J
J
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000502:physiology*; D008297:Male; D009392:Nephrectomy; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D003907:Dexamethasone; D016572:Cyclosporine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat