CHOLESTEROL FEEDING ENHANCES VASOCONSTRICTOR EFFECTS OF PRODUCTS FROMRABBIT POLYMORPHONUCLEAR LEUKOCYTES

We have studied the vasoactive properties of products released from ra bbit polymorphonuclear leukocytes (PMNs) before and after short-term ( 4 and 8 wk) dietary supplementation with 1% cholesterol. Plasma choles terol levels were similar after 4 and 8 wk of cholesterol diet, wherea s gross atherosclerotic lesions were present at 4 wk but significantly more extensive after 8 wk. PMN products from all rabbits caused endot helium-dependent contraction of isolated, control (nonatherosclerotic) rabbit aorta submaximally contracted with phenylephrine. However, bot h 4 and 8 wk of cholesterol feeding resulted in equivalent contraction s by PMN products, which were significantly greater than contractions by control PMNs. Endothelium-dependent contraction (by PMN products) a nd relaxation (by acetylcholine) were attenuated by 8 wk of cholestero l feeding. PMN products attenuated acetylcholine-induced relaxation of aorta from cholesterol-fed rabbits and of control aorta treated with phenoxybenzamine to reduce muscarinic receptor reserve. We conclude th at elevation of plasma cholesterol results in increased release of a P MN product(s) that causes endothelium-dependent constriction.