STEREOSPECIFIC EFFECTS OF EPOXYEICOSATRIENOIC ACIDS ON RENAL VASCULARTONE AND K-CHANNEL ACTIVITY()

The present study examined the effects of 11,12- and 14,15-epoxyeicosa trienoic acids (EETs) on the diameter of small renal arteries of the r at 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 arter ies preconstricted with phenylephrine; however, the S,R-isomer was ina ctive. 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 tetraethyl ammonium (TEA, 1 mM) and iberiotoxin (100 nM), selective inhibitors of the large-conductance Ca2+ activated K+ (K-Ca) channel. In contrast, apamin (100 nM) and 4-aminopyridine (2 mM), which are inhibitors of ot her 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 increa sed outward K+ currents in VSM cells. Addition of the R,S-isomer or ra cemic 11,12-EET (1-100 nM), but not the S,R-isomer, increased the acti vity of K-Ca 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 excise d membrane patches. These results suggest that 11,12-EET is a potent d ilator of small renal arteries and that the R,S-isomer is the active e nantiomer. The vasodilator effect of 11,12-EET appears to involve acti vation of K-Ca channel.