Hydrogen peroxide induces endothelium-dependent and -independent coronary arteriolar dilation: role of cyclooxygenase and potassium channels.

摘要: Hydrogen peroxide, a relatively stable reactive oxygen species, is known to elicit vasodilation, but its underlying mechanism remains elusive. Here, we examined the role of endothelial nitric oxide (NO), prostaglandin, cytochrome P-450-derived metabolites, and smooth muscle potassium channels in coronary arteriolar dilation abluminal H2O2. Pig subepicardial arterioles (50-100 microm) were isolated pressurized without flow for vitro study. Arterioles developed basal tone dilated dose dependently H2O2 (1-100 microM). Disruption th endothelium inhibition cyclooxygenase (COX) by indomethacin produced identical attenuation vasodilation Conversely, was not affected either NO synthase inhibitor NG-nitro-l-arginine methyl ester or P-450 enzyme blocker miconazole. Inhibition COX-1, COX-2 pathway, attenuated H2O2-induced similarly indomethacin. The production prostaglandin E2 (PGE2), I2, from significantly increased Furthermore, PGE2 receptors with AH-6809 similar that In absence functional endothelium, attenuated, an manner, depolarizing agent KCl calcium-activated (KCa) channel iberiotoxin. However, PGE2-induced endothelium-independent also insensitive guanylyl cyclase, lipoxygenase, ATP-sensitive channels, inward rectifier channels. These results suggest induces endothelium-dependent through COX-1-mediated release directly relaxes hyperpolarization KCa activation.