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 Oxid e (NO)-mediated dilation of isolated coronary arterioles to-pharmacological agonists. However, it is not known whether oxLDL specifically affects NO-m ediated dilation-or: generally impairs endothelium-dependent function, incl uding the release of hyperpolarizing factors. In this regard, we investigat ed the dilation of isolated porcine coronary arterioles (50- to 100-mu m lu minal diameter) in response to the activation of various endothelium-depend ent pathways before and after intraluminal incubation of the vessels with o xLDL (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 syntha se (by flow and adenosine), :cyclooxygenase (by arachidonic acid), cytochro me P-450 monooxygenase (by bradykinin), and endothelial membrane hyperpolar ization (by sucrose-induced hyperosmolarity). Incubation of the vessels wit h oxLDL for 60 min did not alter basal tone but did inhibit the vasodilator y responses to increased flow and adenosine in a manner similar to that of the NO synthase inhibitor NG-nitro-L-arginine methyl ester. Vasodilations i n response to flow and adenosine were not affected by intraluminal incubati on 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, hyperosmoti c vasodilation mediated by endothelial hyperpolarization was not affected:b y oxLDL. Endothelium-dependent dilations to the cyclooxygenase activator ar achidonic acid and to the cytochrome P-450 monooxygenase activator bradykin in and endothelium-independent vasodilation to sodium nitroprusside were al so not altered by oxLDL. Collectively, these results;indicate that oxLDL ha s a selective effect on endothelium-dependent dilation with specific impair ment 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 hyp erpolarization of the endothelium.