Vascular smooth muscle cells on matrigel as a model for lps-induced
hypocontractility and no formation.
Li, Shaohua, Sharon X. Fan, and Thomas M. McKenna.
Septic Shock Research Program, Naval Medical Research Institute,
Bethesda, MD 20889
APStracts 3:0297H, 1996.
Treatment of vascular tissue with low levels of lipopolysaccharide
(LPS) induces nitric oxide synthase (NOS) activity and diminishes
vascular contractility. However, in cultured vascular smooth muscle
cells (VSMCs), very high doses of LPS or the combination of LPS with
cytokines are required for the induction of nitric oxide (NO)
formation. The aims of this study were to establish a cell model to
investigate LPS-induced hypocontractility and nitric oxide production
and to test the hypothesis that responses of VSMCs to LPS are
differentiation-regulated. We used Matrigel basement membrane matrix
to maintain VSMC differentiation and found that VSMCs cultured on
Matrigel retained significant contractility in response to KCl
stimulation. Incubation of VSMCs with low levels of LPS (1-100 ng/ml)
induced iNOS mRNA and protein, NO production, and decreased cell
contractility in a time- and dose-dependent fashion. The NOS
inhibitor NG-nitro-L-arginine methyl ester (L-NAME) partially
restored LPS-treated VSMC contractility, while L-arginine reversed
the contractility-restoring effect of L-NAME. These results suggest
that VSMC's grown on Matrigel are a useful experimental model for
investigations into signal transduction mechanisms responsible for
LPS-induced vascular hypocontractility.
Received 10 April 1996; accepted in final form 3 July 1996.
APS Manuscript Number H317-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996