Rapid and reversible inhibition by low density lipoprotein of the endothelium-dependent relaxation to hemostatic substances in porcine coronary arteries. Heat and acid labile factors in low density lipoprotein mediate the inhibition

Abstract

The effects of hemostatic substances on the vascular tone in porcine coronary arteries and the influence of low density lipoprotein on tension were investigated. Thrombin induced a marked concentration-dependent relaxation in prostaglandin F2 alpha-precontracted strips with intact endothelium, whereas it produced a modest constriction in endothelium-denuded arteries. Methylene blue abolished the relaxation, but indomethacin did not affect it significantly. An exposure of the intact strips to low density lipoprotein resulted in a marked inhibition of the relaxation to thrombin but did not interfere with vasodilation by sodium nitroprusside. The inhibition by low density lipoprotein was reversed completely by washing. In contrast, high density lipoprotein lacked such inhibitory effects. Adenosine diphosphate, calcium ionophore A23187, and platelet-activating factor also produced relaxation in the intact strips. An exposure of the strips to low density lipoprotein almost abolished relaxation to these substances. The inhibition was also reversible. Heat treatment or acid treatment of low density lipoprotein resulted in a complete loss of the inhibitory effects, but diisopropyl fluorophosphate treatment did not alter the effect. It is concluded that low density lipoprotein may play a new pathological role in promotion of coronary vasospasm through rapid and reversible inhibition in endothelium-dependent relaxation to hemostatic substances.