oxLDL specifically impairs endothelium-dependent, NO-mediated dilation of coronary arterioles.
Our previous studies implicated that oxidized 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-microm 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 N(G)-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.
Hein
T W
TW
Department of Medical Physiology, Cardiovascular Research Institute, Texas A&M University System Health Science Center, College Station, Texas 77843-1114, USA.
Liao
J C
JC
Kuo
L
L
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009994:Osmolar Concentration; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D016718:Arachidonic Acid; D009569:Nitric Oxide; D000241:Adenosine; D001920:Bradykinin