Barium and 4-aminopyridine inhibit flow-initiated endothelium-independent relaxation.
Although much is known about the underlying mechanism of endothelium-dependent flow-induced vasorelaxation, the cellular processes responsible for the endothelium-independent flow-induced relaxation observed in some vessels is unknown. As there is evidence for the participation of K+ channels in the endothelium-dependent response, the present study was designed to determine whether such channels are involved in the endothelium-independent response and if so, which ones. We examined the effects of various selective K+ channel blockers on endothelium-independent relaxation initiated by intraluminal flow (10-80 microl/min), and by an endothelium-independent vasodilator sodium nitroprusside (SNP, 1 nmol/l to 3 micromol/l) in segments of the rabbit facial vein under isometric conditions. Flow-initiated relaxation was abolished by 25 and 40 mmol/l K+ as well as 10 mmol/l tetraethylammonium (TEA), significantly inhibited by 100 micromol/l Ba2+, 5 mmol/l Cs+ and 7.5 mmol/l 4-aminopyridine (4-AP), but unaffected by 5 micromol/l glibenclamide and 50 nmol/l charybdotoxin. Relaxation induced by SNP was reduced by 7.5 mmol/l 4-AP, but not by any of the above drugs in their listed concentrations. The inhibitory effect of 100 micromol/l Ba2+ on the relaxation caused by low concentrations of K+ (15-20 mmol/l) supports the presence of inward rectifier K+ channels in the vascular smooth muscle cells of this tissue. We speculate that endothelium-independent flow-initiated relaxation of the rabbit facial vein may be associated with activation of inward rectifier and voltage-dependent K+ channels. The latter may also contribute to the vasorelaxation initiated by SNP.
Xie
H
H
Department of Pharmacology, College of Medicine, University of Vermont, Burlington, Vt. 05405-0068, USA.
Bevan
J A
JA
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000494:pharmacology*; D004730:Endothelium, Vascular; D005145:Face / Q000098:blood supply; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D014680:Veins / Q000187:drug effects / Q000502:physiology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D009599:Nitroprusside; D001464:Barium; D015761:4-Aminopyridine; D011188:Potassium