20-hete is an endogenous inhibitor of the large conductance, ca--
-activated, k--channel in renal arterioles.
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, Wisconsin 53226, Clement
Zablocki VA Medical Center, Milwaukee, WI 53205, Department of
Physiology, University of Louisville School of Medicine, Louisville,
KY 40292, Department of Molecular Genetics
APStracts 2:0230R, 1995.
The present study examined the effects of 20-hydroxyeicosatetraenoic
acid (20-HETE) and 17-ODYA, an inhibitor of the metabolism of
arachidonic acid by P450, on K- channel activity in vascular smooth
muscle (VSM) cells isolated from renal arterioles of the rat. Two
types of K- channels were characterized using inside-out, excised
membrane patches. One channel exhibited a large conductance (250.3+/
-5 pS), was activated by membrane depolarization and elevations in
cytoplasmic Ca-- concentration, and was blocked by low concentrations
(<1 mM) of tetraethylammonium (TEA). The other K- channel
exhibited an intermediate conductance (46.3 - 3 pS), was activated by
membrane depolarization but not by changes in intracellular Ca--
concentration, and was blocked by 4-aminopyridine (5 mM). Addition of
20-HETE to the bath (1-100 nM), reduced the frequency of opening of
the large-conductance, Ca---activated, K- channel recorded using
cell-attached patches on VSM cells. It had no effect on the
intermediate conductance K- channel. 17-ODYA (1 [mu]M) increased the
activity of the large-conductance, Ca---activated, K- channel and
this effect was reversed by 20-HETE (10 nM). 20-HETE (1-1000 nM)
reduced the diameter of isolated perfused small renal arteries of the
rat by about 15%. TEA (1 mM) blocked the vasoconstrictor response to
20-HETE (100 nM). These studies suggest that 20-HETE is an
endogenously-formed vasoconstrictor that acts in part by inhibiting
the opening of the large-conductance, Ca---activated, K- channel in
renal arteriolar VSM cells.
Received 28 April 1995; accepted in final form 14 July 1995.
APS Manuscript Number R255-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.