Cholesterol feeding enhances vasoconstrictor effects of products from rabbit polymorphonuclear leukocytes.
We have studied the vasoactive properties of products released from rabbit polymorphonuclear leukocytes (PMNs) before and after short-term (4 and 8 wk) dietary supplementation with 1% cholesterol. Plasma cholesterol levels were similar after 4 and 8 wk of cholesterol diet, whereas gross atherosclerotic lesions were present at 4 wk but significantly more extensive after 8 wk. PMN products from all rabbits caused endothelium-dependent contraction of isolated, control (nonatherosclerotic) rabbit aorta submaximally contracted with phenylephrine. However, both 4 and 8 wk of cholesterol feeding resulted in equivalent contractions by PMN products, which were significantly greater than contractions by control PMNs. Endothelium-dependent contraction (by PMN products) and relaxation (by acetylcholine) were attenuated by 8 wk of cholesterol 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 that elevation of plasma cholesterol results in increased release of a PMN product(s) that causes endothelium-dependent constriction.
Hart
J L
JL
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Sobey
C G
CG
Woodman
O L
OL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000209:etiology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D011817:Rabbits; D012016:Reference Values; D014661:Vasoconstriction / Q000187:drug effects*
D002791:Cholesterol, Dietary; D006454:Hemoglobins; D000109:Acetylcholine