Suppression of K+-induced hyperpolarization by phenylephrine in rat mesenteric artery: relevance to studies of endothelium-derived hyperpolarizing factor
Gr. Richards et al., Suppression of K+-induced hyperpolarization by phenylephrine in rat mesenteric artery: relevance to studies of endothelium-derived hyperpolarizing factor, BR J PHARM, 134(1), 2001, pp. 1-5
In intact mesenteric arteries. increasing [K+](o) by 5 mm hyperpolarized bo
th endothelial and smooth muscle cells. Subsequent exposure to 10 muM pheny
lephrine depolarized both cell types which were then repolarized by a 5 mm
increase in [K+](o) In endothelium-denuded vessels, incieasing [K+](o) by 5
mM hyperpolarized the smooth muscle but K+ had no effect after depolarizat
ion by 10 pm phenylephrine. On subsequent exposure to iberiotoxin plus 4-am
inopyridine, the repolarizing action of 5 mm K+ was restored. In endotheliu
m-intact vessels exposed to phenylephrine. pretreatment with a gap junction
inhibitor (gap 27) reduced K+-mediated smooth muscle repolarization withou
t affecting the endothelial cell response. It is concluded that phenylephri
ne-induced efflux of K+ ria smooth muscle K+ channels produces a local incr
ease in [K+](o) which impairs repolarization to added K+. Thus, studies inv
olving vessels precontracted with agonists which increase [K+](o) maximize
the role of gap junctions and minimize any contribution to the EDHF pathway
from endothelium-derived K+.