Jpn. J. Pharmacol. 70 (2), 149-156 (1996)

Preservation of Endothelium-Dependent Vascular Relaxation in Cholesterol-Fed Mice by the Chronic Administration of Prazosin or Pravastatin

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.

Keywords: Low-density lipoprotein (LDL), Endothelium, Pravastatin, Prazosin, Lysophosphatidylcholine (LPC)

Copyright© The Japanese Pharmacological Society 1996

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