Stereospecific effects of epoxyeicosatrienoic acids on renal
vascular tone and k+-channel activity .
Zou, Ai-Ping, John T. Fleming, John R. Falck, Elizabeth R. Jacobs,
Debebe Gebremedhin, David R. Harder, and Richard J. Roman.
Department of Physiology and Cardiovascular Research Center,
Medical College, of Wisconsin, Milwaukee, WI 53226; Department of
Physiology, University of Louisville School of Medicine, Louisville,
KY 40292; Department of Molecular Genetics, University of Texas
Medical Center, Dallas, TX 75235-9046
APStracts 2:0217F, 1995.
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 TEA (1 mM) and iberiotoxin (100
nM), selective inhibitors of the large conductance, calcium
-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 using 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.
Received 19 June 1995; accepted in final form 29 November 1995.
APS Manuscript Number F194-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 12 December 95