Katsuo Kamata, Satoshi Kojima, Makoto Sugiura and Yutaka Kasuya
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142, Japan
Abstract: The relaxation of aortic rings in response to acetylcholine (ACh) was significantly decreased in cholesterol-fed mice. The attenuated relaxation in cholesterol-fed mice was preserved by the chronic administration of prazosin (20 mg/kg/day) or pravastatin (12.5 mg/kg/day). Serum low-density lipoprotein (LDL) levels were significantly increased in mice given cholesterol. The increased serum LDL levels in cholesterol-fed mice were returned to normal by the chronic administration of prazosin and pravastatin. A prior incubation of aortic rings with lysophosphatidylcholine (LPC) significantly attenuated ACh- and A23187-induced endothelium-dependent relaxation. The inhibitory effects of LPC on endothelium-dependent relaxation were not affected by indomethacin or superoxide dismutase. The sodium nitroprusside-induced relaxation of aortic rings was not changed by LPC. The inhibitory effects on ACh-induced relaxation by NG-monomethyl-L-arginine were restored by a prior exposure to L-arginine, whereas the inhibition of endothelium-dependent relaxation by LPC was not affected by L-arginine. These results suggest that cholesterol-fed mice are useful animal models of hypercholesterolemia, and chronic administration of prazosin or pravastatin can preserve endothelium-dependent relaxation by lowering serum LDL in these animals. It is further suggested that LPC derived from oxidized LDL may be involved in the reduced endothelium-dependent relaxation in hyperlipidemia.
Low-density lipoprotein (LDL), Endothelium, Pravastatin, Prazosin, Lysophosphatidylcholine (LPC)
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