Inhibition of nitric oxide synthesis increases erythrocyte membrane fluidity and unsaturated fatty acid content

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.