Oxidized low-density lipoproteins inhibit endothelium-dependent relaxations in isolated large and small rabbit coronary arteries.
1. Previous studies suggest that oxidatively modified low-density lipoproteins (oxLDL) contribute to the impairment of endothelium-dependent vasodilation in the large arteries of hypercholesterolaemic animals, whereas this may not be the case with regard to the impairment of coronary resistance vessels. For this reason, the effect of lipoproteins on coronary resistance arteries has been examined in this study. 2. The influence of lipoproteins on endothelium-dependent relaxation induced by acetylcholine (ACh) or sodium nitroprusside in PGF2 alpha-preconstricted rings from the large (1st order branch) and small coronary arteries (3rd order branch) and the aorta of New Zealand White rabbits, was investigated. 3. The sensitivity to ACh was greater in the large compared with the small diameter coronary arteries. 4. Endothelium-dependent relaxations were unaffected by native LDL. Oxidized LDL (0.5 and 1 mg protein mL-1) caused a reversible inhibition of relaxations in both preconstricted small and large coronary arteries which was overcome at high ACh concentrations. Similar inhibitions were found in the aorta. 5. Endothelium-independent relaxations elicited by sodium nitroprusside in the large and small coronary arteries were unaffected by the oxidized lipoproteins, indicating that soluble guanylate cyclase activity was unaltered. 6. It is concluded that inhibition of endothelium-dependent relaxation in the small diameter coronary arteries in hypercholesterolaemia may arise from products of oxidative modification of LDL present in the artery itself or released upstream from proximal lesions.
Buckley
C
C
Department of Pharmacology, Royal Free Hospital School of Medicine, London, UK.
Bund
S J
SJ
McTaggart
F
F
Bruckdorfer
K R
KR
Oldham
A
A
Jacobs
M
M
D000109:Acetylcholine / Q000633:toxicity; D000818:Animals; D001011:Aorta / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009213:Myography; D009599:Nitroprusside / Q000633:toxicity; D010084:Oxidation-Reduction; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects
D008077:Lipoproteins, LDL; D009599:Nitroprusside; D015237:Dinoprost; D000109:Acetylcholine