Effect of nitric oxide synthase inhibitors on endothelial [ca2+[
cb]i and microvessel permeability.
He, P., B. Liu, and F. E. Curry.
Department of Human Physiology, School of Medicine, University of
California, Davis, CA 95616
APStracts 3:0309H, 1996.
To investigate the mechanism whereby nitric oxide (NO) signaling
pathways regulate microvessel permeability in vivo, we measured
changes in microvessel hydraulic conductivity (Lp) and endothelial
cytoplasmic calcium concentration, [Ca2+]i, in response to calcium
ionophore, ionomycin (IM, 5 [mu]M), and ATP (10 [mu]M) before and
after the use of NO synthase (NOS) inhibitors in single perfused frog
mesenteric venular microvessels. IM induced a transient increase in
endothelial [Ca2+]i and an associated increase in Lp. The NOS
inhibitors Nw-nitro-L-arginine methyl ester (L-name, 10 and 300
[mu]M) and Nw-monomethyl-L-arginine (L-nmma, 10, 50, and 100 [mu]M)
significantly attenuated the peak increase in Lp induced by IM. A
similar inhibitory effect was also observed on the increase in Lp
mediated by ATP. In contrast, D-nmma, a biologically inactive isomer
of L-nmma, showed no effect on IM-induced increase in Lp. L-arginine
(3 mM) reversed the inhibitory effect of L-nmma (10 [mu]M) on Lp.
However, the NOS inhibitors did not alter the magnitude and time
course of the biphasic increase in endothelial [Ca2+]i induced by
both IM and ATP. These data suggest that (1) calcium-dependent NO
release is a necessary step to increase microvessel permeability, and
(2) the action of NOS inhibitors in attenuating the permeability
increase in response to IM and ATP occurs downstream from calcium
entry and does not involve modification of the initial increase in
endothelial [Ca2+]i.
Received 23 January 1996; accepted in final form 28 June 1996.
APS Manuscript Number H179-6.
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