Activation of vascular BK channels by XXXX is dependent on cytochrome P450 epoxygenase activity.

@entity5204 @entity19191 @entity4600 @entity73328 @entity1474 @entity4601 @entity460 @entity972 @entity35
AIMS: n-3 @entity1474 ( @entity5204 ) are known to protect the cardiovascular system and improve blood pressure control. These important dietary constituents are converted into bioactive metabolites, but their role in regulation of the cardiovascular system is unclear. In particular, the functions of the cytochrome P450 (CYP) metabolites of n-3 @entity5204 remain virtually unexplored. In this study, we examined the effects of @entity4600 ( @entity4601 ) on the regulation of large-conductance @entity460 -activated @entity972 (BK) channel activities in coronary arterial smooth muscle cells. METHODS AND RESULTS: Using whole-cell patch-clamp techniques, we found that @entity4601 is a potent activator of BK currents in @entity35 coronary arterial smooth muscle cells with an EC(50) of 0.23    0.03   M. This effect was abolished by pre-incubation with the CYP epoxygenase inhibitor, SKF525A (10   M). The effects of @entity4601 on the BK channels were reproduced by @entity73328 (16,17-EpDPE) with an EC(50) of 19.7    2.8 nM. The physiological role of the CYP metabolites of @entity4601 was confirmed by measuring @entity4601 -mediated vasodilatation in isolated @entity35 coronary arteries. @entity4601 dilated pressurized isolated coronary arteries in a dose-dependent manner, and the @entity4601 effects were abolished after pre-treatment with SKF525A (10   M) or with iberiotoxin (100 nM). In addition, 16,17-EpDPE directly produced coronary vasodilatation that was @entity19191 sensitive. CONCLUSION: These results suggest that @entity4601 -mediated vasodilatation is mediated through CYP epoxygenase metabolites by activation of vascular BK channels.
