ACUTE EXPOSURE TO CHOLESTEROL INCREASES ARTERIAL NITROPRUSSIDE-MEDIATED 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 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.