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      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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> as well as 10 mmol/l tetraethylammonium (TEA), significantly inhibited by 100 µmol/l Ba<sup>2+</sup>, 5 mmol/l Cs<sup>+</sup> 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 Ba<sup>2+</sup> on the relaxation caused by low concentrations of K<sup>+</sup> (15–20 mmol/l) supports the presence of inward rectifier K<sup>+</sup> 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<sup>+</sup> channels. The latter may also contribute to the vasorelaxation initiated by SNP.

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          Most cited references 2

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          Haemodynamic shear stress activates a K+ current in vascular endothelial cells.

          The endothelial lining of blood vessels is subjected to a wide range of haemodynamically-generated shear-stress forces throughout the vascular system. In vivo and in vitro, endothelial cells change their morphology and biochemistry in response to shear stress in a force- and time-dependent way, or when a critical threshold is exceeded. The initial stimulus-response coupling mechanisms have not been identified, however. Recently, Lansman et al. described stretch-activated ion channels in endothelial cells and suggested that they could be involved in the response to mechanical forces generated by blood flow. The channels were relatively nonselective and were opened by membrane stretching induced by suction. Here we report whole-cell patch-clamp recordings of single arterial endothelial cells exposed to controlled levels of laminar shear stress in capillary flow tubes. A K+ selective, shear-stress-activated ionic current (designated Ik.s) was identified which is unlike previously described stretch-activated currents. Ik.s varies in magnitude and duration as a function of shear stress (half-maximal effect at 0.70 dyn cm-2), desensitizes slowly and recovers rapidly and fully on cessation of flow. Ik.s activity represents the earliest and fastest stimulus-response coupling of haemodynamic forces to endothelial cells yet found. We suggest that localized flow-activated hyperpolarization of endothelium involving Ik.s may participate in the regulation of vascular tone.
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            The pharmacology of potassium channels and their therapeutic potential.


              Author and article information

              J Vasc Res
              Journal of Vascular Research
              S. Karger AG
              December 1998
              23 September 2008
              : 35
              : 6
              : 428-436
              Department of Pharmacology, College of Medicine, University of Vermont, Burlington, Vt., USA
              25614 J Vasc Res 1998;35:428–436
              © 1998 S. Karger AG, Basel

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              Page count
              Figures: 7, References: 38, Pages: 9
              Research Paper


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