Hydrogen peroxide selectively reduces vasoconstriction caused by thromboxane A 2 mimetic U46619

Hydrogen peroxide (H 2 O 2 ) can function as an endothelium‐derived hyperpolarizing factor (EDHF) and thromboxane A 2 , as an endothelium‐derived constricting factor (EDCF). However, their interaction has not been studied previously. Recent studies have shown that H 2 O 2 stabilizes the thromboxane A 2 (TP) receptor by translocating it to the Golgi complex. Therefore, we investigated mouse cremaster arterioles in vivo (n=8) before and after 15–20 min of H 2 O 2 . Exposure to H 2 O 2 reduced basal vascular tone of mouse cremaster arterioles in vivo (baseline diameter increased by 10±4%). H 2 O 2 (10 −5 M) inhibited constriction to U46619 (10 −7 to 10 −5 M). At the maximal concentration, U46619‐induced constriction was reduced by 78±14% (p < 0.001) compared to the control. In contrast, H 2 O 2 did not significantly attenuate the vasoconstrictor responses to angiotensin II (−7±6%) or phenylephrine (−3±13%). These results demonstrate a selective inhibition of the response of vascular TP receptors by H 2 O 2 . Thus, in addition to facilitating vascular relaxation via EDHF, at high concentrations, H 2 O 2 can block vasoconstriction via EDCF by selectively inhibiting the effect of vasoconstrictor prostaglandins. (Supported by AHA 0230308N and HL 68686‐01)