Faculty Collaboration Database

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

05/01/1996

Pubmed ID

8928844

DOI

10.1152/ajprenal.1996.270.5.F822

Scopus ID

2-s2.0-0029888211 (requires institutional sign-in at Scopus site)   195 Citations

Abstract

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 RJ

Authors

David Harder PhD, MS Emeritus Professor in the Physiology department at Medical College of Wisconsin
Elizabeth R. Jacobs MD Emeritus Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

8,11,14-Eicosatrienoic Acid
Animals
Calcium
Electric Conductivity
Muscle Tonus
Muscle, Smooth, Vascular
Patch-Clamp Techniques
Potassium Channels
Rats
Rats, Sprague-Dawley
Renal Artery
Stereoisomerism
Vasoconstriction