Barium and 4-aminopyridine inhibit flow-initiated endothelium-independent relaxation

Although much is known about the underlying mechanism of endothelium depend ent flow-induced vasorelaxation, the cellular processes responsible for the endothelium-independent flow-induced relaxation observed in some vessels i s unknown. As there is evidence for the participation of K+ channels in the endothelium-dependent response, the present study was designed to determin e whether such channels are involved in the endothelium-independent respons e and if so, which ones. We examined the effects of various selective KC ch annel blockers on endothelium-independent relaxation initiated by intralumi nal flow (10-80 mu l/min), and by an endothelium-independent vasodilator so dium nitroprusside (SNP, 1 nmol/l to 3 mu mol/l) in segments of the rabbit facial vein under isometric conditions. Flow-initiated relaxation was aboli shed by 25 and 40 mmol/l K+ as well as 10 mmol/l tetraethylammonium (TEA), significantly inhibited by 100 mu mol/l Ba2+, 5 mmol/l Cs+ and 7.5 mmol/l 4 -aminopyridine (4-AP), but unaffected by 5 mu mol/l glibenclamide and 50 nm ol/l charybdotoxin. Relaxation induced by SNP was reduced by 7.5 mmol/l 4-A P, but not by any of the above drugs in their listed concentrations. The in hibitory effect of 100 mu mol/l Ba2+ on the relaxation caused by low concen trations of K+ (15-20 mmol/l) supports the presence of inward rectifier Kchannels in the vascular smooth muscle cells of this tissue. We speculate t hat endothelium-independent flow-initiated relaxation of the rabbit facial vein may be associated with activation of inward rectifier and voltage-depe ndent K+ channels. The latter may also contribute to the vasorelaxation ini tiated by SNP.