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 lipop roteins (oxLDL) contribute to the impairment of endothelium-dependent vasodilation in the large arteries of hypercholesterolaemic animals, w hereas this may not be the case with regard to the impairment of coron ary resistance vessels. For this reason, the effect of lipoproteins on coronary resistance arteries has been examined in this study. 2 The i nfluence of lipoproteins on endothelium-dependent relaxation induced b y acetylcholine (ACh) or sodium nitroprusside in PGF(2 alpha)-preconst ricted rings from the large (1st order branch) and small coronary arte ries (3rd order branch) and the aorta of New Zealand White rabbits, wa s investigated. 3 The sensitivity to ACh was greater in the large comp ared with the small diameter coronary arteries. 4 Endothelium-dependen t relaxations were unaffected by native LDL. Oxidized LDL (0.5 and 1 m g protein mL(-1)) caused a reversible inhibition of relaxations in bot h preconstricted small and large coronary arteries which was overcome at high ACh concentrations. Similar inhibitions were found in the aort a. 5 Endothelium-independent relaxations elicited by sodium nitropruss ide in the large and small coronary arteries were unaffected by the ox idized lipoproteins, indicating that soluble guanylate cyclase activit y was unaltered. 6 It is concluded that inhibition of endothelium-depe ndent relaxation in the small diameter coronary arteries in hyperchole sterolaemia may arise from products of oxidative modification of LDL p resent in the artery itself or released upstream from proximal lesions .