Preservation of endothelium-dependent vascular relaxation in cholesterol-fed mice by the chronic administration of prazosin or pravastatin.
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.
Kamata
K
K
Department of Physiology and Morphology, Hoshi University, Tokyo, Japan.
Kojima
S
S
Sugiura
M
M
Kasuya
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002784:Cholesterol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017035:Pravastatin / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D002784:Cholesterol; D017035:Pravastatin; D000109:Acetylcholine; D011224:Prazosin