Effect of low density lipoproteins on vascular reactivity

: Investigations of circulation in humans and various animal models demonstrate changes in the reactivity of atherosclerotic arteries. Both attenuation of endothelium-dependent vasodilations and enhancement of contractile responses to different contractile agonists have been described. Recent in vitro studies provide evidence that low-density lipoproteins (LDL) accumulating in atherosclerotic arteries are involved in the mechanisms responsible for these changes. Perfusion of isolated arteries with native and oxidatively modified LDL results in attenuation of endothelium-dependent dilations. Furthermore, oxidized LDL impairs dilations to endothelium-independent agonists, and potentiates agonist-induced contractile responses. These in vitro observations are in accordance with alterations of the reactivity of arteries obtained from cholesterol fed rabbits. In these atherosclerotic arteries, contractile responses to the same agonists as used in the in vitro studies were enhanced, and endothelium-dependent dilations were attenuated. The extent of these changes was positively correlated with the degree of intimal atherosclerotic plaques, thus, with the regions containing oxidized LDL. Therefore, accumulation of oxidized LDL in atherosclerotic arteries may lead to an imbalance of vascular tonus regulation which favors inadequate vasoconstriction.