Effect of Ox-LDL on endothelium-dependent response in pig ciliary artery: prevention by an ET(A) antagonist.
OBJECTIVE
To investigate whether oxidized low-density lipoprotein (Ox-LDL) affects endothelium-dependent responses in isolated porcine ciliary arteries.


METHODS
In a myograph system for isometric force measurements, quiescent vessels were incubated with 50 microg/ml, 100 microg/ml, or 200 microg/ml Ox-LDL; 100 microg/ml native LDL (n-LDL); 1 microM of the ET(A)- endothelin receptor antagonist BQ 123; 100 microg/ml Ox-LDL coadministered with 1 microM BQ 123; or 100 microg/ml Ox-LDL coadministered with 50 microM of the protein synthesis inhibitor cycloheximide. Vessels with nonfunctional endothelium (intentionally and mechanically damaged) were also exposed to 100 microg/ml Ox-LDL. Two hours later, vessels were washed, precontracted with the thromboxane A2 analog U 46619 (approximately 0.1 microM), and exposed to bradykinin (0.1 nM to 3 microM), an endothelium-dependent relaxing agent.


RESULTS
In quiescent vessels, Ox-LDL evoked delayed contractions. In contrast, no contractions were observed after exposure to n-LDL, BQ 123, Ox-LDL with BQ 123, or Ox-LDL with cycloheximide. In vessels with nonfunctional endothelium, Ox-LDL did not evoke contraction. Bradykinin-induced relaxations were inhibited in a dose-dependent manner by Ox-LDL, but not by n-LDL, BQ 123 alone, Ox-LDL with BQ 123, or Ox-LDL with cycloheximide.


CONCLUSIONS
In porcine ciliary arteries, Ox-LDL affects endothelium-dependent responses through the activation of ET(A)- endothelin receptors. As Ox-LDL can accumulate in atherosclerotic plaques, such a mechanism might be involved in the occlusion of the ophthalmic circulation observed in patients with hypercholesterolemia and atherosclerosis.
Zhu
P
P
Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic, Basel, Switzerland.
Dettmann
E S
ES
Resink
T J
TJ
Lüscher
T F
TF
Flammer
J
J
Haefliger
I O
IO
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D019842:Ciliary Arteries / Q000187:drug effects* / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007537:Isometric Contraction / Q000502:physiology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010084:Oxidation-Reduction; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004338:Drug Combinations; D065128:Endothelin Receptor Antagonists; D008077:Lipoproteins, LDL; D010456:Peptides, Cyclic; D011500:Protein Synthesis Inhibitors; D014662:Vasoconstrictor Agents; C099252:oxidized low density lipoprotein; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003513:Cycloheximide; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D001920:Bradykinin