TY - JOUR
T1 - EET homologs potently dilate coronary microvessels and activate BKCa channels
AU - Zhang, Yongde
AU - Oltman, Christine L.
AU - Lu, Tong
AU - Lee, Hon Chi
AU - Dellsperger, Kevin C.
AU - Vanrollins, Mike
PY - 2001
Y1 - 2001
N2 - Epoxyeicosatrienoic acids (EETs) are released from endothelial cells and potently dilate small arteries by hyperpolarizing vascular myocytes. In the present study, we investigated the structural specificity of EETs in dilating canine and porcine coronary microvessels (50-140 μm ID) and activating large-conductance Ca2+-activated K+ (BKca) channels. The potencies and efficacies of EET regioisomers and enantiomers were compared with those of two EET homologs: Epoxyeicosaquatraenoic acids (EEQs), which are made from eicosapentaenoic acid by the same cytochrome P-450 epoxygenase that generates EETs from arachidonic acid, and epoxydocosatetraenoic acids (EDTs), which are EETs that are two carbons longer. With ECso values of 3-120 pM but without regio- or stereoselectivity, EETs potently dilated canine and porcine microvessels. Surprisingly, the EEQs and EDTs had comparable potencies and efficacies in dilating microvessels. Moreover, 50 nM 13,14-EDT activated the BKCa channels with the same efficacy as either 11,12-EET enantiomer at 50 nM. We conclude that coronary microvessels and BKCa channels possess low structural specificity for EETs and suggest that EEQs and EDTs may thereby also be endothelium-derived hyper-polarizing factors.
AB - Epoxyeicosatrienoic acids (EETs) are released from endothelial cells and potently dilate small arteries by hyperpolarizing vascular myocytes. In the present study, we investigated the structural specificity of EETs in dilating canine and porcine coronary microvessels (50-140 μm ID) and activating large-conductance Ca2+-activated K+ (BKca) channels. The potencies and efficacies of EET regioisomers and enantiomers were compared with those of two EET homologs: Epoxyeicosaquatraenoic acids (EEQs), which are made from eicosapentaenoic acid by the same cytochrome P-450 epoxygenase that generates EETs from arachidonic acid, and epoxydocosatetraenoic acids (EDTs), which are EETs that are two carbons longer. With ECso values of 3-120 pM but without regio- or stereoselectivity, EETs potently dilated canine and porcine microvessels. Surprisingly, the EEQs and EDTs had comparable potencies and efficacies in dilating microvessels. Moreover, 50 nM 13,14-EDT activated the BKCa channels with the same efficacy as either 11,12-EET enantiomer at 50 nM. We conclude that coronary microvessels and BKCa channels possess low structural specificity for EETs and suggest that EEQs and EDTs may thereby also be endothelium-derived hyper-polarizing factors.
KW - Coronary microcirculation
KW - Cytochrome P-450 epoxygenases
KW - N-3 and n-6 polyunsaturated fatty acids
UR - http://www.scopus.com/inward/record.url?scp=0034979365&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034979365&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.2001.280.6.h2430
DO - 10.1152/ajpheart.2001.280.6.h2430
M3 - Article
C2 - 11356595
AN - SCOPUS:0034979365
SN - 0363-6135
VL - 280
SP - H2430-H2440
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6 49-6
ER -