Oxidized low-density lipoprotein inhibits nitric oxide-mediated coronary arteriolar dilation by up-regulating endothelial arginase I. Academic Article uri icon


  • Oxidized low-density lipoprotein (OxLDL) causes impairment of endothelium-dependent, nitric oxide (NO)-mediated vasodilation involving l-arginine deficiency. However, the underlying mechanism remains elusive. Since arginase and endothelial NO synthase (eNOS) share the substrate l-arginine, we hypothesized that OxLDL may reduce l-arginine availability to eNOS for NO production, and thus vasodilation, by up-regulating arginase. To test this hypothesis, porcine subepicardial arterioles (70-130 m) were isolated for vasomotor study and for immunohistochemical detection of arginase and eNOS expressions. The coronary arterioles dilated dose-dependently to the endothelium-dependent NO-mediated vasodilator serotonin. This vasodilation was inhibited in the same manner by NOS inhibitor N(G)-nitro-l-arginine methyl ester and by lumenal OxLDL (0.5 mg protein/mL). The inhibitory effect of OxLDL was reversed after treating the vessels with either l-arginine (3 mM) or arginase inhibitor difluoromethylornithine (DFMO; 0.4 mM). Consistent with vasomotor alterations, OxLDL inhibited serotonin-induced NO release from coronary arterioles and this inhibition was reversed by DFMO. Vascular arginase activity was significantly elevated by OxLDL. Immunohistochemical analysis indicated that OxLDL increased arginase I expression in the vascular wall without altering eNOS expression. Taken together, these results suggest that OxLDL up-regulates arginase I, which contributes to endothelial dysfunction by reducing l-arginine availability to eNOS for NO production and thus vasodilation.

published proceedings

  • Microcirculation

author list (cited authors)

  • Wang, W., Hein, T. W., Zhang, C., Zawieja, D. C., Liao, J. C., & Kuo, L.

citation count

  • 36

complete list of authors

  • Wang, Wei||Hein, Travis W||Zhang, Cuihua||Zawieja, David C||Liao, James C||Kuo, Lih

publication date

  • January 2011