April 1999
Volume 40, Issue 5
Free
Articles  |   April 1999
Effect of Ox-LDL on endothelium-dependent response in pig ciliary artery: prevention by an ET(A) antagonist.
Author Affiliations
  • P Zhu
    Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic, Basel, Switzerland.
  • E S Dettmann
    Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic, Basel, Switzerland.
  • T J Resink
    Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic, Basel, Switzerland.
  • T F Lüscher
    Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic, Basel, Switzerland.
  • J Flammer
    Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic, Basel, Switzerland.
  • I O Haefliger
    Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic, Basel, Switzerland.
Investigative Ophthalmology & Visual Science April 1999, Vol.40, 1015-1020. doi:
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      P Zhu, E S Dettmann, T J Resink, T F Lüscher, J Flammer, I O Haefliger; Effect of Ox-LDL on endothelium-dependent response in pig ciliary artery: prevention by an ET(A) antagonist.. Invest. Ophthalmol. Vis. Sci. 1999;40(5):1015-1020.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

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.

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