EET homologs potently dilate coronary microvessels and activate BKCa channels

Epoxyeicosatrienoic acids (EETs) are released from endothelial cells and po tently dilate small arteries by hyperpolarizing vascular myocytes. In the p resent study, we investigated the structural specificity of EETs in dilatin g canine and porcine coronary microvessels (50-140 mum ID) and activating l arge-conductance Ca2+-activated K+ (BKCa) channels. The potencies and effic acies of EET regioisomers and enantiomers were compared with those of two E ET homologs: epoxyeicosaquatraenoic acids (EEQs), which are made from eicos apentaenoic acid by the same cytochrome P-450 epoxygenase that generates EE Ts from arachidonic acid, and epoxydocosatetraenoic acids (EDTs), which are EETs that are two carbons longer. With EC50 values of 3-120 pM but without regio- or stereoselectivity, EETs potently dilated canine and porcine micr ovessels. Surprisingly, the EEQs and EDTs had comparable potencies and effi cacies in dilating microvessels. Moreover, 50 nM 13,14-EDT activated the BK Ca channels with the same efficacy as either 11,12-EET enantiomer at 50 nM. We conclude that coronary microvessels and BKCa channels possess low struc tural specificity for EETs and suggest that EEQs and EDTs may thereby also be endothelium-derived hyperpolarizing factors.