Effect of Ox-LDL on endothelium-dependent response in pig ciliary artery: prevention by an ET(A) antagonist.

PURPOSE 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.