Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Jan;105(1):216–222. doi: 10.1111/j.1476-5381.1992.tb14237.x

Oxidative modification of low-density lipoproteins and the inhibition of relaxations mediated by endothelium-derived nitric oxide in rabbit aorta.

F Plane 1, K R Bruckdorfer 1, P Kerr 1, A Steuer 1, M Jacobs 1
PMCID: PMC1908615  PMID: 1596684

Abstract

1. The mechanism by which Cu(2+)-oxidized low-density lipoproteins (oxLDL) inhibit acetylcholine (ACh)-evoked relaxations mediated by endothelium-derived nitric oxide (EDRF) in rabbit aortic rings was investigated. The proposed role of lysophosphatidylcholine (LPC) in the inhibition was also studied. 2. The kinetics of lipid peroxidation of native low-density lipoproteins (LDL) from individual donors, as measured by changes in conjugated diene concentration, were related to the inhibitory effects of the resultant oxLDL. It was found that the more susceptible LDL was to oxidation, the greater the inhibition. 3. No correlation was found between the inhibitory effects of oxLDL and LPC content. 4. Synthetic 1-palmitoyl LPC produced an inhibition of ACh-induced relaxations and when added to precontracted rings evoked nitric oxide-mediated endothelium-dependent relaxation. This latter effect was not elicited by oxLDL. 5. Synthetic 1-palmitoyl (10 microM) had no effect on relaxations evoked by glyceryl trinitrate in endothelium-denuded aortic rings in contrast to the inhibition found previously for oxLDL. 6. Concentrations of oxLDL and phospholipase A2-treated LDL which inhibited relaxation contained very different LPC concentrations. Unlike oxLDL, the inhibitory effects of phospholipase A2-treated LDL preparations were independent of the donors and showed no lag period. 7. We suggest that there are differences in the mechanisms by which oxLDL and 1-palmitoyl LPC exert their inhibitory effects on relaxation. 8. The inhibition of relaxation by oxLDL (1-2 mg protein ml-1) was prevented by the presence of high-density lipoproteins (HDL; 1-2 mg protein ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
216

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  2. Cooke J. P., Andon N. A., Girerd X. J., Hirsch A. T., Creager M. A. Arginine restores cholinergic relaxation of hypercholesterolemic rabbit thoracic aorta. Circulation. 1991 Mar;83(3):1057–1062. doi: 10.1161/01.cir.83.3.1057. [DOI] [PubMed] [Google Scholar]
  3. Esterbauer H., Dieber-Rotheneder M., Waeg G., Striegl G., Jürgens G. Biochemical, structural, and functional properties of oxidized low-density lipoprotein. Chem Res Toxicol. 1990 Mar-Apr;3(2):77–92. doi: 10.1021/tx00014a001. [DOI] [PubMed] [Google Scholar]
  4. Esterbauer H., Jürgens G., Quehenberger O., Koller E. Autoxidation of human low density lipoprotein: loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes. J Lipid Res. 1987 May;28(5):495–509. [PubMed] [Google Scholar]
  5. Esterbauer H., Striegl G., Puhl H., Rotheneder M. Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun. 1989;6(1):67–75. doi: 10.3109/10715768909073429. [DOI] [PubMed] [Google Scholar]
  6. Galle J., Mülsch A., Busse R., Bassenge E. Effects of native and oxidized low density lipoproteins on formation and inactivation of endothelium-derived relaxing factor. Arterioscler Thromb. 1991 Jan-Feb;11(1):198–203. doi: 10.1161/01.atv.11.1.198. [DOI] [PubMed] [Google Scholar]
  7. Hessler J. R., Morel D. W., Lewis L. J., Chisolm G. M. Lipoprotein oxidation and lipoprotein-induced cytotoxicity. Arteriosclerosis. 1983 May-Jun;3(3):215–222. doi: 10.1161/01.atv.3.3.215. [DOI] [PubMed] [Google Scholar]
  8. Hessler J. R., Robertson A. L., Jr, Chisolm G. M., 3rd LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture. Atherosclerosis. 1979 Mar;32(3):213–229. doi: 10.1016/0021-9150(79)90166-7. [DOI] [PubMed] [Google Scholar]
  9. Jacobs M., Plane F., Bruckdorfer K. R. Native and oxidized low-density lipoproteins have different inhibitory effects on endothelium-derived relaxing factor in the rabbit aorta. Br J Pharmacol. 1990 May;100(1):21–26. doi: 10.1111/j.1476-5381.1990.tb12045.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kugiyama K., Kerns S. A., Morrisett J. D., Roberts R., Henry P. D. Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Nature. 1990 Mar 8;344(6262):160–162. doi: 10.1038/344160a0. [DOI] [PubMed] [Google Scholar]
  11. POOLE J. C., SANDERS A. G., FLOREY H. W. The regeneration of aortic endothelium. J Pathol Bacteriol. 1958 Jan;75(1):133–143. doi: 10.1002/path.1700750116. [DOI] [PubMed] [Google Scholar]
  12. Rosenfeld M. E., Khoo J. C., Miller E., Parthasarathy S., Palinski W., Witztum J. L. Macrophage-derived foam cells freshly isolated from rabbit atherosclerotic lesions degrade modified lipoproteins, promote oxidation of low-density lipoproteins, and contain oxidation-specific lipid-protein adducts. J Clin Invest. 1991 Jan;87(1):90–99. doi: 10.1172/JCI115006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Saito T., Wolf A., Menon N. K., Saeed M., Alves C., Bing R. J. Lysolecithins as endothelium-dependent vascular smooth muscle relaxants that differ from endothelium-derived relaxing factor (nitric oxide) Proc Natl Acad Sci U S A. 1988 Nov;85(21):8246–8250. doi: 10.1073/pnas.85.21.8246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Shimokawa H., Vanhoutte P. M. Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolemia and atherosclerosis. Circ Res. 1989 May;64(5):900–914. doi: 10.1161/01.res.64.5.900. [DOI] [PubMed] [Google Scholar]
  15. Simon B. C., Cunningham L. D., Cohen R. A. Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery. J Clin Invest. 1990 Jul;86(1):75–79. doi: 10.1172/JCI114718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Skipski V. P., Peterson R. F., Barclay M. Quantitative analysis of phospholipids by thin-layer chromatography. Biochem J. 1964 Feb;90(2):374–378. doi: 10.1042/bj0900374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Smith E. B., Ashall C. Low-density lipoprotein concentration in interstitial fluid from human atherosclerotic lesions. Relation to theories of endothelial damage and lipoprotein binding. Biochim Biophys Acta. 1983 Dec 20;754(3):249–257. doi: 10.1016/0005-2760(83)90139-x. [DOI] [PubMed] [Google Scholar]
  18. Sparrow C. P., Parthasarathy S., Steinberg D. A macrophage receptor that recognizes oxidized low density lipoprotein but not acetylated low density lipoprotein. J Biol Chem. 1989 Feb 15;264(5):2599–2604. [PubMed] [Google Scholar]
  19. Steinberg D., Parthasarathy S., Carew T. E., Khoo J. C., Witztum J. L. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989 Apr 6;320(14):915–924. doi: 10.1056/NEJM198904063201407. [DOI] [PubMed] [Google Scholar]
  20. Thomas C. E., Jackson R. L. Lipid hydroperoxide involvement in copper-dependent and independent oxidation of low density lipoproteins. J Pharmacol Exp Ther. 1991 Mar;256(3):1182–1188. [PubMed] [Google Scholar]
  21. Verbeuren T. J., Jordaens F. H., Zonnekeyn L. L., Van Hove C. E., Coene M. C., Herman A. G. Effect of hypercholesterolemia on vascular reactivity in the rabbit. I. Endothelium-dependent and endothelium-independent contractions and relaxations in isolated arteries of control and hypercholesterolemic rabbits. Circ Res. 1986 Apr;58(4):552–564. doi: 10.1161/01.res.58.4.552. [DOI] [PubMed] [Google Scholar]
  22. Vita J. A., Treasure C. B., Nabel E. G., McLenachan J. M., Fish R. D., Yeung A. C., Vekshtein V. I., Selwyn A. P., Ganz P. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation. 1990 Feb;81(2):491–497. doi: 10.1161/01.cir.81.2.491. [DOI] [PubMed] [Google Scholar]
  23. Weisgraber K. H., Mahley R. W. Subfractionation of human high density lipoproteins by heparin-Sepharose affinity chromatography. J Lipid Res. 1980 Mar;21(3):316–325. [PubMed] [Google Scholar]
  24. Yokoyama M., Hirata K., Miyake R., Akita H., Ishikawa Y., Fukuzaki H. Lysophosphatidylcholine: essential role in the inhibition of endothelium-dependent vasorelaxation by oxidized low density lipoprotein. Biochem Biophys Res Commun. 1990 Apr 16;168(1):301–308. doi: 10.1016/0006-291x(90)91708-z. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES