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- W2017369531 abstract "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 to abluminal H 2 O 2 . Pig subepicardial coronary arterioles (50–100 μm) were isolated and pressurized without flow for in vitro study. Arterioles developed basal tone and dilated dose dependently to H 2 O 2 (1–100 μM). Disruption of th endothelium and inhibition of cyclooxygenase (COX) by indomethacin produced identical attenuation of vasodilation to H 2 O 2 . Conversely, the vasodilation to H 2 O 2 was not affected by either the NO synthase inhibitor N G -nitro-l-arginine methyl ester or the cytochrome P-450 enzyme blocker miconazole. Inhibition of the COX-1, but not the COX-2 pathway, attenuated H 2 O 2 -induced dilation similarly to indomethacin. The production of prostaglandin E 2 (PGE 2 ), but not prostaglandin I 2 , from coronary arterioles was significantly increased by H 2 O 2 . Furthermore, inhibition of PGE 2 receptors with AH-6809 attenuated vasodilation to H 2 O 2 similar to that produced by indomethacin. In the absence of a functional endothelium, H 2 O 2 -induced dilation was attenuated, in an identical manner, by a depolarizing agent KCl and a calcium-activated potassium (K Ca ) channel inhibitor iberiotoxin. However, PGE 2 -induced dilation was not affected by iberiotoxin. The endothelium-independent dilation to H 2 O 2 was also insensitive to the inhibition of guanylyl cyclase, lipoxygenase, ATP-sensitive potassium channels, and inward rectifier potassium channels. These results suggest that H 2 O 2 induces endothelium-dependent vasodilation through COX-1-mediated release of PGE 2 and also directly relaxes smooth muscle by hyperpolarization through K Ca channel activation." @default.
- W2017369531 created "2016-06-24" @default.
- W2017369531 creator A5050151730 @default.
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- W2017369531 date "2003-12-01" @default.
- W2017369531 modified "2023-10-16" @default.
- W2017369531 title "Hydrogen peroxide induces endothelium-dependent and -independent coronary arteriolar dilation: role of cyclooxygenase and potassium channels" @default.
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- W2017369531 doi "https://doi.org/10.1152/ajpheart.00487.2003" @default.
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