Acute exposure to cholesterol increases arterial nitroprusside- and endothelium-mediated relaxation.
The effect of cholesterol enrichment on arterial relaxation was studied by evaluating sodium nitroprusside (SNP)- and endothelium-mediated relaxation of isolated rabbit carotid artery. Arterial segments were perfused in vitro (4 h) with cholesterol-rich liposomes consisting of free cholesterol (FC) and phospholipid (PL) in a 2:1 molar ratio. Ring segments from arteries exposed to cholesterol-rich liposomes exhibited a 60% increase (P < 0.01) in FC content without affecting PL content. Cholesterol-enrichment was associated with a twofold increase (r = 0.92, P < 0.05) in acetylcholine- and A23187-induced endothelium-mediated relaxation. Bioassay of endothelium-derived relaxing factor(s) (EDRF) after cholesterol exposure indicated that EDRF half-life and/or release increased (P < 0.05) threefold. A trend (P = 0.07) toward increased smooth muscle cell sensitivity to EDRF after cholesterol enrichment was also observed. Cholesterol enrichment increased (P < 0.05) sensitivity to SNP 12-fold, and this difference was further augmented (P < 0.01) twofold with endothelium removal. Cholesterol enrichment had no effect on relaxation to N2,2'-O-dibutyrylguanosine 3',5'-cyclic monophosphate. These data indicate that acute cholesterol enrichment increases EDRF activity from arterial endothelium and increases smooth muscle responses to both EDRF and SNP.
Bialecki
R A
RA
Department of Physiology and Biochemistry, Medical College of Pennsylvania, Philadelphia 19129.
Tulenko
T N
TN
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002784:Cholesterol / Q000494:pharmacology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D050356:Lipid Metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D009599:Nitroprusside; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; D002784:Cholesterol