Inhibitors of actin filament polymerisation attenuate force but not global intracellular calcium in isolated pressurised resistance arteries

Linda Shaw, Shabbir Ahmed, Clare Austin, Michael J Taggart

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Receptor-coupled contractile activation of arterial smooth muscle involves increases in intracellular calcium ([Ca(2+)](i)) 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(2+)](i) and force responsiveness of pressurised rat mesenteric arteries to alpha-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(2+)](i) 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(2+)](i) 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(2+)](i) 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(2+)](i) homeostasis, to regulate the smooth muscle contractile state.

Original languageEnglish
Pages (from-to)1-10; discussion 10
JournalJournal of Vascular Research
Volume40
Issue number1
DOIs
Publication statusPublished - 20 Mar 2003

Keywords

  • Actin Cytoskeleton/drug effects
  • Actins/antagonists & inhibitors
  • Animals
  • Blood Pressure
  • Bridged Bicyclo Compounds, Heterocyclic/pharmacology
  • Calcium/analysis
  • Cytochalasin D/pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Fluorescent Dyes
  • Indoles
  • Male
  • Mesenteric Arteries
  • Muscle Contraction/drug effects
  • Muscle, Smooth/physiology
  • Muscle, Smooth, Vascular/chemistry
  • Phenylephrine/pharmacology
  • Polymers/metabolism
  • Portal Vein
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha/drug effects
  • Thiazoles/pharmacology
  • Thiazolidines
  • Uterus
  • Vascular Resistance

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