Beta-migrating very low density lipoprotein attenuates endothelium-dependent relaxation in rabbit atherosclerotic aortas.
We studied the effects of beta-migrating very low density lipoprotein (beta-VLDL) on the vascular responses of isolated thoracic aortic preparations taken from normal and hypercholesterolemic rabbits. The endothelium-dependent relaxation induced by acetylcholine or adenosine triphosphate (ATP) was attenuated in the arteries from hypercholesterolemic rabbits that were fed a cholesterol-rich diet for 12 weeks. In these aortas, the lesional circumference of the atherosclerotic plaques (fatty streaks) was only 12.18 +/- 1.98%. The relaxation induced by the Ca2+ ionophore A23187 or nitroglycerin was not altered. Preincubation with beta-VLDL significantly inhibited the relaxation due to acetylcholine, ATP, or A23187, especially in the aortas of hypercholesterolemic rabbits. However, beta-VLDL did not alter the response to nitroglycerin. Preincubation with high density lipoprotein had no significant effect on vessel relaxation. These results indicated that endothelium-dependent relaxation was already inhibited in the early stages of atherosclerosis, and that the atherogenic lipoprotein, beta-VLDL, further inhibited endothelium-dependent relaxation in atherosclerotic aortas. It may be that beta-VLDL also plays a role in determining the level of vascular tonus in atherosclerosis.
Hayashi
T
T
Department of Geriatrics, Nagoya University School of Medicine, Japan.
Naito
M
M
Ishikawa
T
T
Kuzuya
M
M
Funaki
C
C
Tateishi
T
T
Asai
K
K
Hidaka
H
H
Kuzuya
F
F
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D001018:Aortic Diseases / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology*; D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology; D006937:Hypercholesterolemia / Q000150:complications; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits
D008077:Lipoproteins, LDL; D009569:Nitric Oxide; D000001:Calcimycin; D000255:Adenosine Triphosphate; D005996:Nitroglycerin; D000109:Acetylcholine; D009638:Norepinephrine