Gc. Wellman et Ja. Bevan, BARIUM INHIBITS THE ENDOTHELIUM-DEPENDENT COMPONENT OF FLOW BUT NOT ACETYLCHOLINE-INDUCED RELAXATION IN ISOLATED RABBIT CEREBRAL-ARTERIES, The Journal of pharmacology and experimental therapeutics, 274(1), 1995, pp. 47-53
An increase in blood flow can cause vasodilation through a local actio
n on the blood vessel walt. We examined the involvement of potassium c
hannels in the relaxation of segments of the rabbit middle cerebral ar
tery to intraluminal infusion of physiological saline. In segments wit
h intact endothelium, intraluminal flow (20 mu l/min) produced a relax
ation of 81.7 +/- 3.0% of pre-flow tone. This relaxation was significa
ntly reduced upon endothelium removal (43%, n = 5) or inhibition of ni
tric oxide synthase (34%, n = 6). Inhibition of nitric oxide synthase
had no effect on the relaxation in endothelium denuded preparations. T
his suggests that the overall response to flow is a combination of end
othelium/nitric oxide dependent and smooth muscle components. Barium c
hloride (10 and 300 mu M) reduced flow-induced relaxations by 30 and 6
1%, respectively, in intact arteries but had no effect following endot
helium removal or nitric oxide synthase inhibition. Micromolar concent
rations of barium are thought to block selectively the inward rectifie
r potassium channel. These concentrations of barium were without effec
t on the relaxation produced by the endothelium-dependent vasodilator
acetylcholine. Blockers of other potassium channels, glibenclamide (10
mu M, ATP-sensitive K+ channel), charybdotoxin (100 nN) and tetraethy
lammonium (0.3 mM, Ca++-activated K+ channel) and 4-aminopyridine(1 mM
, delayed rectifier K+ channel) did not effect either endothelium-depe
ndent or endothelium-independent flow-induced relaxation. Our results
suggest that flow-induced shear stress activates endothelial cell inwa
rd rectifier potassium channels leading to increased synthesis/release
of nitric oxide. This mechanism is distinct from that involved with t
he acetylcholine-stimulated release of nitric oxide, and may be the me
chanism behind Row-induced release of endothelial-derived relaxing fac
tors observed in vivo.