Effect of Ox-LDL on endothelium-dependent response in pig ciliary artery: Prevention by an ETA antagonist

PURPOSES. To investigate whether oxidized low-density lipoprotein (Ox-LDL) affects endothelium-dependent responses in isolated porcine ciliary arterie s. METHODS. In a myograph system for isometric force measurements, quiescent v essels were incubated with 50 mu g/ml, 100 mu g/ml, or 200 mu g/ml Ox-LDL; 100 mu g/ml native LDL (n-LDL); 1 mu M of the ETA- endothelin receptor anta gonist BQ 123; 100 mu g/ml Ox-LDL coadministered with 1 mu M BQ 123; or 100 mu g/ml Ox-LDL coadministered with 50 mu M of the protein synthesis inhibi tor cycloheximide. Vessels with nonfunctional endothelium (intentionally an d mechanically damaged) were also exposed to 100 mu g/ml Ox-LDL. Two hours later, vessels were washed, precontracted with the thromboxane A, analog U 46619 (approximate to 0.1 mu M), and exposed to bradykinin (0.1 nM to 3 mu M), an endothelium-dependent relaxing agent. RESULTS. in quiescent vessels, Ox-LDL evoked delayed contractions. In contr ast, 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 en dothelium, 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-depend ent responses through the activation of ETA- endothelin receptors. As Ox-LD L can accumulate in atherosclerotic plaques, such a mechanism might be invo lved in the occlusion of the ophthalmic circulation observed in patients wi th hypercholesterolemia and atherosclerosis.