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 action on the blood vessel wall. We examined the involvement of potassium channels in the relaxation of segments of the rabbit middle cerebral artery to intraluminal infusion of physiological saline. In segments with intact endothelium, intraluminal flow (20 microliters/min) produced a relaxation of 81.7 +/- 3.0% of pre-flow tone. This relaxation was significantly reduced upon endothelium removal (43%, n = 5) or inhibition of nitric oxide synthase (34%, n = 6). Inhibition of nitric oxide synthase had no effect on the relaxation in endothelium denuded preparations. This suggests that the overall response to flow is a combination of endothelium/nitric oxide dependent and smooth muscle components. Barium chloride (10 and 300 microM) reduced flow-induced relaxations by 30 and 61%, respectively, in intact arteries but had no effect following endothelium removal or nitric oxide synthase inhibition. Micromolar concentrations of barium are thought to block selectively the inward rectifier potassium channel. These concentrations of barium were without effect on the relaxation produced by the endothelium-dependent vasodilator acetylcholine. Blockers of other potassium channels, glibenclamide (10 microM, ATP-sensitive K+ channel), charybdotoxin (100 nN) and tetraethylammonium (0.3 mM, Ca(++)-activated K+ channel) and 4-aminopyridine (1 mM, delayed rectifier K+ channel) did not effect either endothelium-dependent or endothelium-independent flow-induced relaxation. Our results suggest that flow-induced shear stress activates endothelial cell inward rectifier potassium channels leading to increased synthesis/release of nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)
Wellman
G C
GC
Department of Pharmacology, Vermont Center for Vascular Research, College of Medicine, University of Vermont, Burlington, USA.
Bevan
J A
JA
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology*; D019806:Cromakalim; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits
D017609:Barium Compounds; D001578:Benzopyrans; D002712:Chlorides; D026902:Potassium Channel Blockers; D011758:Pyrroles; D019806:Cromakalim; C024986:barium chloride; D009599:Nitroprusside; D000109:Acetylcholine