Upregulation of arginase by H2O2 impairs endothelium-dependent nitric oxide-mediated dilation of coronary arterioles. Academic Article uri icon


  • OBJECTIVE: Overproduction of reactive oxygen species such as hydrogen peroxide (H2O2) has been implicated in various cardiovascular diseases. However, mechanism(s) underlying coronary vascular dysfunction induced by H2O2 is unclear. We studied the effect of H2O2 on dilation of coronary arterioles to endothelium-dependent and endothelium-independent agonists. METHODS AND RESULTS: Porcine coronary arterioles were isolated and pressurized without flow for in vitro study. All vessels developed basal tone and dilated dose-dependently to activators of nitric oxide (NO) synthase (adenosine and ionomycin), cyclooxygenase (arachidonic acid), and cytochrome P450 monooxygenase (bradykinin). Intraluminal incubation of vessels with H2O2 (100 micromol/L, 60 minutes) did not alter basal tone but inhibited vasodilations to adenosine and ionomycin in a manner similar as that by NO synthase inhibitor L-NAME. H2O2 affected neither endothelium-dependent responses to arachidonic acid and bradykinin nor endothelium-independent dilation to sodium nitroprusside. The inhibited adenosine response was not reversed by removal of H2O2 but was restored by excess L-arginine. Inhibition of L-arginine consuming enzyme arginase by alpha-difluoromethylornithine or N(omega)-hydroxy-nor-L-arginine also restored vasodilation. Administering deferoxamine, an inhibitor of hydroxyl radical production, prevented the H2O2-induced impairment of vasodilation to adenosine. Western blot and reverse-transcription polymerase chain reaction results indicated that arginase I was upregulated after treating vessels with H2O2. CONCLUSIONS: H2O2 specifically impairs endothelium-dependent NO-mediated dilation of coronary microvessels by reducing L-arginine availability through upregulation of arginase. The formation of hydroxyl radicals from H2O2 may contribute to this process.

published proceedings

  • Arterioscler Thromb Vasc Biol

author list (cited authors)

  • Thengchaisri, N., Hein, T. W., Wang, W., Xu, X., Li, Z., Fossum, T. W., & Kuo, L.

citation count

  • 84

complete list of authors

  • Thengchaisri, Naris||Hein, Travis W||Wang, Wei||Xu, Xin||Li, Zhenbo||Fossum, Theresa W||Kuo, Lih

publication date

  • September 2006