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.


METHODS
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 micrograms/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 N omega-nitro-L-arginine (L-NNA, 5 x 10(-5) to 10(-4) mol/l), a potent and selective inhibitor of NO synthase.


CONCLUSIONS
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.
Institute of Pharmacology and Toxicology, Academy of Medical Sciences, Kiev, Ukraine.
A I
AI
Soloviev
A V
AV
Stefanov
O V
OV
Bazilyuk
V F
VF
Sagach
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008081:Liposomes / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*
D008081:Liposomes; D010713:Phosphatidylcholines; D009569:Nitric Oxide; D000109:Acetylcholine