oxLDL specifically impairs endothelium-dependent, NO-mediated dilation of coronary arterioles

Our previous studies implicated thatoxidized low-density lipoprotein (oxLDL), a putative atherogenic agent, impairs endothelium-dependent, nitric Oxide (NO)-mediated dilation of isolated coronary arterioles to-pharmacological agonists. However, it is not known whether oxLDL specifically affects NO-mediated dilation-or: generally impairs endothelium-dependent function, including the release of hyperpolarizing factors. In this regard, we investigated the dilation of isolated porcine coronary arterioles (50- to 100-mu m luminal diameter) in response to the activation of various endothelium-dependent pathways before and after intraluminal incubation of the vessels with oxLDL (0.5 mg: protein/ml for 60 min). In the absence of oxLDL, all vessels developed basal tone and dilated in response to the activation of NO synthase (by flow and adenosine), :cyclooxygenase (by arachidonic acid), cytochrome P-450 monooxygenase (by bradykinin), and endothelial membrane hyperpolarization (by sucrose-induced hyperosmolarity). Incubation of the vessels with oxLDL for 60 min did not alter basal tone but did inhibit the vasodilatory responses to increased flow and adenosine in a manner similar to that of the NO synthase inhibitor NG-nitro-L-arginine methyl ester. Vasodilations in response to flow and adenosine were not affected by intraluminal incubation of the vessels with either a vehicle solution or the native LDL (0.5 mg protein/ml, 60 min). In contrast with the NO-mediated response, hyperosmotic vasodilation mediated by endothelial hyperpolarization was not affected:by oxLDL. Endothelium-dependent dilations to the cyclooxygenase activator arachidonic acid and to the cytochrome P-450 monooxygenase activator bradykinin and endothelium-independent vasodilation to sodium nitroprusside were also not altered by oxLDL. Collectively, these results;indicate that oxLDL has a selective effect on endothelium-dependent dilation with specific impairment of the NO-mediated :response, whereas cyclooxygenase and cytochrome P-450 monooxygenase-mediated dilations are spared from this inhibitory effect. In addition, oxLDL does not appear to:affect vasodilation mediated by hyperpolarization of the endothelium.