PHOSPHOLIPID-VESICLES (LIPOSOMES) RESTORE ENDOTHELIUM-DEPENDENT CHOLINERGIC RELAXATION IN THORACIC AORTA FROM SPONTANEOUSLY HYPERTENSIVE RATS

Objective: The present study was designed to examine, using isolated preparations of thoracic aorta, the effects of artificial phosphatidylcholine vesicles (liposomes) on vascular endothelium-dependent responses in spontaneously hypertensive rats (SHR) compared with those in Wistar-Kyoto (WKY) normotensive rats. Design: Phosphatidylcholine liposomes, which possess the ability to repair the plasma membrane of living cells, were used in these experiments. Methods: Liposomes were prepared from egg phosphatidylcholine. A suspension of lipid was subjected to ultrasound treatment at 20-degrees-C at a frequency of 44 kHz for 45 s. The contraction of vascular smooth muscle was recorded using a force-displacement transducer coupled with a physiograph. Results: It was shown that aortic smooth muscle from SHR demonstrated a loss of endothelium-dependent relaxation in acetylcholine (10(-6) mol/l) compared with WKY rat aortic smooth muscle. Liposomes in a concentration of 100-125 mug/ml restored these endothelium-dependent responses more effectively than L-arginine (10(-5) to 10(-4) mol/l), which is known to be a precursor of endothelium-derived relaxing factor (EDRF). This effect was not observed in denuded aortic rings, and liposomes lost their ability of repairing endothelium-dependent vascular relaxant responses in the presence of methylene blue (5 x 10(-5) mol/l), which inhibits soluble guanylyl cyclase activation by nitric oxide (NO), and Nomega)-nitro-L-arginine (L-NNA, 5 x 10(-5) to 10(-4) mol/l), a potent and selective inhibitor of NO synthase. Conclusion: The present results suggest that the loss of vascular endothelium-dependent responses in SHR may be, at least partly, due to endothelial cells membrane damage, and that the phosphatidylcholine liposomes can repair the function of endothelial cells and restore synthesis or release, or both, of EDRF in hypertension.