Stereospecific effects of epoxyeicosatrienoic acids on renal vascular tone and K(+)-channel activity. Am J Physiol 1996 May;270(5 Pt 2):F822-32
Date
05/01/1996Pubmed ID
8928844DOI
10.1152/ajprenal.1996.270.5.F822Scopus ID
2-s2.0-0029888211 (requires institutional sign-in at Scopus site) 191 CitationsAbstract
The present study examined the effects of 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) on the diameter of small renal arteries of the rat and assessed their action on K(+)-channel activity in vascular smooth muscle (VSM) cells isolated from these vessels. The R,S-isomer of 11,12-EET (1, 10, and 100 nM) increased the diameter of small renal arteries preconstricted with phenylephrine; however, the S,R-isomer was inactive. Both the R,S- and S,R-isomers of 14,15-EET had little effect on the diameter of these vessels even at a high concentration (100 nM). The vasodilator effect of 11(R),12(S)-EET was attenuated by tetraethylammonium (TEA, 1 mM) and iberiotoxin (100 nM), selective inhibitors of the large-conductance Ca(2+)-activated K+ (KCa) channel. In contrast, apamin (100 nM) and 4-aminopyridine (2 mM), which are inhibitors of other types of K+ channels, had no effect on the vasodilatory effect of 11,12-EET. In patch-clamp experiments, 100 nM racemic 11,12-EET increased outward K+ currents in VSM cells. Addition of the R,S-isomer or racemic 11,12-EET (1-100 nM), but not the S,R-isomer, increased the activity of KCa channel recorded from renal VSM cells with cell-attached patches. However, racemic EET had no effect on this channel when added to the internal (inside-out) or external (outside-out) face of excised membrane patches. These results suggest that 11,12-EET is a potent dilator of small renal arteries and that the R,S-isomer is the active enantiomer. The vasodilator effect of 11,12-EET appears to involve activation of KCa channel.
Author List
Zou AP, Fleming JT, Falck JR, Jacobs ER, Gebremedhin D, Harder DR, Roman RJMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAnimals
Calcium
Electric Conductivity
Muscle Tonus
Muscle, Smooth, Vascular
Patch-Clamp Techniques
Potassium Channels
Rats
Rats, Sprague-Dawley
Renal Artery
Stereoisomerism
Vasoconstriction
