Am. Dorrance et al., Inhibition of nitric oxide synthesis increases erythrocyte membrane fluidity and unsaturated fatty acid content, AM J HYPERT, 13(11), 2000, pp. 1194-1202
Changes in the lipid composition of the membrane affect its fluidity and fu
nction. These variables are altered in various forms of hypertension. Our h
ypothesis was that the rapid increase in blood pressure (BP) caused by inhi
bition of nitric oxide production would lead to alterations in membrane flu
idity similar to those observed in genetic hypertension. We used N-omega-ni
tro L-arginine methyl ester (L-NAME) and vehicle-treated (3 weeks) Wistar-K
yoto rats to study the effects of nitric oxide synthase (NOS) inhibition on
membrane fluidity and lipid composition. Erythrocyte membrane fluidity was
measured by fluorescence anisotropy. Membrane lipids were separated using
Sep-Pak and thin-layer chromatography. Fatty acid methyl esters were produc
ed and analyzed by gas chromatography-mass spectrometry. N-omega-nitro L-ar
ginine methyl ester treatment increased BP and erythrocyte membrane fluidit
y. The phospholipid and unsaturated fatty acid levels in the membranes from
the L-NAME-treated rats were consistent with the increase in fluidity (ie,
more unsaturated fatty acid, in particular, arachidonic and docosahexaenoi
c acid) and a reduction in membrane sphingomyelin content. Fatty acid analy
sis of individual lipid groups suggested the changes in membrane fatty acid
composition may be asymmetric, with the majority of the changes occurring
in the outer leaflet. Inhibition of NOS results in changes in membrane comp
osition that may explain the concurrent changes in fluidity. The increased
membrane fluidity observed here contrasts with the reduced fluidity observe
d in genetic hypertension or unchanged fluidity in secondary hypertension.
The effects could be related to NOS inhibition or may be a direct effect of
L-NAME. Am J Hypertens 2000;13:1194-1202 (C) 2000 American Journal of Hype
rtension, Ltd.