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      Inhibitors of Actin Filament Polymerisation Attenuate Force but Not Global Intracellular Calcium in Isolated Pressurised Resistance Arteries


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          Receptor-coupled contractile activation of arterial smooth muscle involves increases in intracellular calcium ([Ca<sup>2+</sup>]<sub>i</sub>) and subsequent alteration of myosin light chain phosphorylation. An additional mechanism whereby agonists could regulate vascular contractility may be alteration of actin filament dynamics. Therefore, in this study, we have investigated the influence of two inhibitors of actin filament polymerisation, cytochalasin D and latrunculin B, on the [Ca<sup>2+</sup>]<sub>i</sub> and force responsiveness of pressurised rat mesenteric arteries to α-adrenergic stimulation. Following cytochalasin D or latrunculin B treatment, phenylephrine-induced constrictions were significantly reduced to 11 ± 3.2% (n = 6) and 10 ± 4.4% (n = 6) of control, respectively, whereas [Ca<sup>2+</sup>]<sub>i</sub> remained at 98 ± 21% and 104 ± 7.0% of control, respectively. Such effects of cytochalasin D were not restricted to mesenteric small arteries. Cytochalasin D also significantly reduced the force, but not [Ca<sup>2+</sup>]<sub>i</sub> responses to agonist stimulation in other vascular (portal vein) and non-vascular (uterine) tissues. These data indicate that inhibitors of net actin polymerisation attenuate maximum agonist-induced force responsiveness without similar reductions in [Ca<sup>2+</sup>]<sub>i</sub> in pressurised resistance vessels and other smooth muscle tissues. This suggests that modulation of the dynamic equilibrium between filamentous F-actin and monomeric globular actin (G-actin) may be an important mechanism, acting independently of global [Ca<sup>2+</sup>]<sub>i</sub> homeostasis, to regulate the smooth muscle contractile state.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          February 2003
          26 March 2003
          : 40
          : 1
          : 1-10
          aSmooth Muscle Physiology Group, Cardiovascular Research, University of Manchester, Manchester Royal Infirmary, bMaternal and Fetal Health Research Centre, Human Development and Reproductive Health Research, University of Manchester, St. Mary’s Hospital, Manchester, UK
          68940 J Vasc Res 2003;40:1–10
          © 2003 S. Karger AG, Basel

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          Page count
          Figures: 6, References: 33, Pages: 10
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