Barium and 4-Aminopyridine Inhibit Flow-Initiated Endothelium-Independent Relaxation

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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 µl/min), and by an endothelium-independent vasodilator sodium nitroprusside (SNP, 1 nmol/l to 3 µmol/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 µmol/l Ba²⁺, 5 mmol/l Cs⁺ and 7.5 mmol/l 4-aminopyridine (4-AP), but unaffected by 5 µmol/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 µmol/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.