Inhibition of nitric oxide synthesis increases venular permeability
and alters endothelial actin cytoskeleton.
Baldwin, Ann L., Gavin Thurston, and Hamda Al Naemi.
Department of Physiology, College of Medicine, University of
Arizona, Tucson, Arizona 85724-5051. Department of Anatomy,
University of California, San Francisco, CA 94143-0452
APStracts 5:0064H, 1998.
Inhibition of nitric oxide (NO) synthesis using NG-nitro-L-arginine
methyl ester (L-NAME), or NG-monomethyl-L-arginine (L-NMMA) increases
venular permeability in the rat mesentery (10), but the cellular
mechanisms of this response are not known. This study was performed
to determine whether such venular leaks are associated with changes
in the endothelial actin cytoskeleton. In anesthetized Sprague Dawley
rats, the microvasculature of a mesenteric window was perfused with
buffered saline, with or without 10-5 M L-NAME, L-NMMA or the
inactive enantiomer, (D-NAME), for 3 or 30 minutes. Fluoroscein
isothiocyanate (FITC)-albumin was added to the perfusate for the last
3 minutes. The vasculature was perfusion-fixed, stained for
filamentous actin, and for mast cells, and viewed microscopically. In
control preparations, venules showed few FITC-albumin leaks and the
endothelial actin cytoskeleton consisted of a peripheral rim along
the cell-cell junctions. Preparations treated with L-NAME or L-NMMA
showed significantly more leakage, the actin rims in leaky venules
were discontinuous, and short, randomly-oriented fibers appeared
within the cells. In non-leaky venules, the peripheral actin rims
sometimes contained small, equally-spaced discontinuities, not seen
in control preparations. Although a mast cell stabilizer was used,
27-70 % of the mast cells were degranulated in the presence of L
-NMMA. Thus, inhibition of NO synthesis alters the endothelial
cytoskeleton and increases albumin leakage from mesenteric venules,
either directly, or indirectly via the involvement of mast cells.
Received 13 August 1997; accepted in final form 3 February 1998.
APS Manuscript Number H767-7.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 19 February 1998