Regulation of endothelial nitric oxide synthase expression by
cyclosporin a in bovine aortic endothelial cells.
L[acute]opez-Ongil, S., M. Saura, D. Rodr[acute]iguez-Puyol, M.
Rodr[acute]iguez-Puyol, S. Lamas.
Departments of Physiology and Pharmacology and Medicine,
Alcal[acute]a de Henares University, Nephrology Section, Hospital
Pr[acute]incipe de Asturias and Centro de Investigaciones
Biol[acute]ogicas, C.S.I.C., Madrid, Spain
APStracts 3:0110H, 1996.
Cyclosporin A (CsA) is considered a cornerstone advance in
immunosuppresion. However, serious side effects such as hypertension
have fostered an important body of research regarding their
pathophysiology. Although the participation of several vasoactive
factors in the hypertensive response has been described, recent
attention has been driven to endothelial-derived vasoactive factors
and several reports describe an overproduction of endothelin-1 (ET-1)
and a deficient endothelial-dependent vasodilation. Concerning the
latter, no definitive clues for the precise molecular mechanisms have
been provided. We now demonstrate that endothelial cells in culture
synthesize more NO in the presence of CsA for 24 hours in a
concentration-response manner. This augmentation is correlated with a
3-fold increase in the ecNOS transcript which is time-dependent and
maximal at 24 hours. The CsA-induced increase in ecNOS mRNA
expression was blocked by actinomycin D, but unaltered by
cycloheximide. Levels of ecNOS protein were also enhanced by CsA
after 24 hours. These data establish that NO synthesis is moderately
enhanced in endothelial cells exposed to CsA for long periods of
time, and describe a new mode of regulating ecNOS gene expression.
Received 12 June 1995; accepted in final form 6 March 1996.
APS Manuscript Number H532-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96