20-HETE IS AN ENDOGENOUS INHIBITOR OF THE LARGE-CONDUCTANCE CA2-ACTIVATED K+ CHANNEL IN RENAL ARTERIOLES()

The present study examined the effects of 20-hydroxyeicosatetraenoic a cid (20-HETE) and 17-octadecynoic acid (17-ODYA), an inhibitor of the metabolism of arachidonic acid by P-450, on K+-channel activity in vas cular smooth muscle cells (VSM) isolated from renal arterioles of the rat. Two types of K+ channels were characterized using inside-out exci sed membrane patches. One channel exhibited a large conductance (250.3 +/- 5 pS), was activated by membrane depolarization and elevations in cytoplasmic Ca2+ concentration, and was blocked by low concentrations (<1 mM) of tetraethylammonium (TEA). The other K+ channel exhibited a n intermediate conductance (46.3 +/- 3 pS), was activated by membrane depolarization but not by changes in intracellular Ca2+ 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-conduc tance Ca2+-activated K+ channel recorded using cell-attached patches o n VSM. It had no effect on the intermediate-conductance K+ channel. 17 -ODYA (1 mu M) increased the activity of the large-conductance Ca2+-ac tivated K+ channel, and this effect was reversed by 20-HETE (10 nM). 2 0-HETE (1-1000 nM) reduced the diameter of isolated perfused small ren al arteries of the rat by similar to 15%. TEA (1 mM) blocked the vasoc onstrictor response to 20-HETE (100 nM). These studies suggest that 20 -HETE is an endogenously formed vasoconstrictor that acts in part by i nhibiting the opening of the large-conductance Ca2+-activated K+ chann el in renal arteriolar VSM.