Dexamethasone increases enos gene expression and prevents renal
vasoconstriction induced by cyclosporine.
Bobadilla, Norma A., Edilia Tapia, Fabiola Jim[acute]enez, Laura G.
S[acute]anchez-Lozada, Jos[acute]e Santamar[acute]ia, Alberto
Monjard[acute]in, Alexis Bolio, Gerardo Gamba, and Jaime Herrera
-Acosta.
1Department of Nephrology, Instituto Nacional de Cardiolog[acute]ia
Ignacio Ch[acute]avez and 2Molecular Physiology Unit, Instituto
Nacional de la Nutrici[acute]on Salvador Zubir[acute]an and Instituto
de Investigaciones Biom[acute]edicas, National University of
Mexico
APStracts 6:0120F, 1999.
Cyclosporin (CsA) induced renal vasoconstriction (RV) is attributed to
an imbalance in vasoactive factors release. Dexamethasone (Dexa)
exerts a renal vasodilatory effect by a mechanism not characterized.
This study evaluates if Dexa effect is mediated by NO and if it
prevents CsA induced RV. Micropuncture studies were performed in six
groups of uninephrectomized rats treated for 7 days with: vehicle
(V); V + Dexamethasone 4 mg/kg (V+Dexa); CsA 30 mg/kg, CsA+Dexa, V+L
-NAME 10 mg/kg, and V+Dexa+L-NAME. NOS isoforms mRNA-levels were
evaluated in renal cortex and medulla by semiquantitative-RT-PCR
analysis in the first four groups. Dexa produced renal vasodilation,
which was blocked by concomitant L-NAME administration, Dexa effect
was associated with higher cortical and medullary endothelial-NOS
(eNOS) and cortical inducible-NOS (iNOS) mRNA-levels. In CsA group,
Dexa 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 expression.
We conclude that Dexa 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.
Received 15 December 1998; accepted in final form 4 June 1999.
APS Manuscript Number F327-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 25 June 1999