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Role of intermediate conductance Ca2+ -activated potassium channels in no-mediated modulation of vasoconstriction in rat mesenteric resistance arteries
Abstract   Peer reviewed

Role of intermediate conductance Ca2+ -activated potassium channels in no-mediated modulation of vasoconstriction in rat mesenteric resistance arteries

P M Kerr, Shaun L Sandow, J M Baserman, D Welsh, W C Cole and F Plane
Journal of Vascular Research, Vol.45(Supplement 1), p.53
International Symposium on Resistance Arteries (ISRA), 9th (Hamilton Island, Australia, 17-Feb-2008–21-Feb-2008)
2008
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Abstract

Medical and Health Sciences vascular smooth muscle cells
Introduction: Contractile activation of vascular smooth muscle cells is limited by the release of endothelium-derived relaxing factors such as nitric oxide (NO), although the underlying mechanisms are as yet unclear. We have investigated the role of intermediate conductance Ca2+-activated potassium (IKCa) channels in NO-mediated modulation of phenylephrine (PE)-evoked constriction in rat mesenteric resistance arteries. Methods: Third order mesenteric arteries were mounted in either a wire myograph or a pressure myograph as previously described.1 Results: Pre-incubation with either L-NAME (NO synthase inhibitor;100 μM; 30 mins) or TRAM-34 (5 μM; 10 mins; IKCa inhibitor) significantly potentiated PE-evoked contractions in endotheliumintact segments of rat mesenteric artery (n=5-6) mounted in a wire myograph. The effects of L-NAME and TRAM-34 were not additive (n=5-6) and these inhibitors did not alter PE-evoked responses in endothelium-denuded arteries (n=5-6). Similarly, addition of L-NAME to the inside or the outside of endothelium-intact segments of mesenteric artery mounted in a pressure myograph, potentiated constrictions to PE (n=4). In contrast, TRAM-34 enhanced PE-evoked constriction when applied to the outside of the arteries but not when applied to the lumen (n=3-4). Application of xestospongin (10 μM), a non-selective antagonist at inositol triphosphate receptors (IP3R), to the lumen of pressurized rat mesenteric arteries also potentiated constrictions to PE (n=3). Subsequent addition of either L-NAME or TRAM-34 did not further increase PE-evoked responses (n=4). Ultrastructural immunohistochemistry demonstrated localization of IKCa at holes in the internal elastic lamina associated with myoendothelial gap junctions and accumulation of IP3R within endothelial cell projections in these arteries. Pre-incubation with either L-NAME or TRAM-34 significantly inhibited relaxations to Ach (n=10) in arterial segments mounted in a wire myograph. The magnitude of inhibition caused by Tram-34 was not significantly different from that caused by L-NAME (n=6-10) and the effects of the two inhibitors were not additive. Pre-incubation with apamin (50 nM), an inhibitor of SKCa, did not significantly alter Ach-evoked relaxation (n=6). However, in the presence of either LNAME or Tram-34, application of apamin reduced the maximum relaxation to Ach by around 80% (n=6-12; P less than 0.01). Addition of L-NAME, apamin and TRAM-34 together did not cause further significant inhibition of relaxation (n=6-12: P>0.05). TRAM-34 and apamin did not alter relaxations evoked by the NO donor diethylamine NONOate (n=4; P>0.05).Conclusion: These data indicate that endothelial IKCa modulate production and/or release of NO in rat mesenteric arteries. Activation of endothelial IKCa and IP3R by transfer of Ca2+ and/or IP3 from underlying smooth muscle cells may underlie NO-dependent modulation of vasoconstriction in these vessels.

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