BARIUM INHIBITS THE ENDOTHELIUM-DEPENDENT COMPONENT OF FLOW BUT NOT ACETYLCHOLINE-INDUCED RELAXATION IN ISOLATED RABBIT CEREBRAL-ARTERIES

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.