title: Force suppression and the crossbridge cycle in swine carotid artery.
abstract: Cyclic nucleotides can relax arterial smooth muscle without reductions in crossbridge phosphorylation, a process termed force suppression. There are two potential mechanisms for force suppression: 1) phosphorylated crossbridges binding to thin filaments could be inhibited or 2) the attachment of thin filaments to anchoring structures could be disrupted. These mechanisms were evaluated by comparing histamine-stimulated swine arterial smooth muscle with and without forskolin-induced force suppression and with and without latrunculin-A-induced actin filament disruption. At matched force, force suppression was associated with higher crossbridge phosphorylation and shortening velocity at low loads when compared with tissues without force suppression. Shortening velocity at high loads, noise temperature, hysteresivity, and stiffness did not differ with and without force suppression. These data suggest that crossbridge phosphorylation regulates the crossbridge cycle during force suppression. Actin disruption with latrunculin-A was associated with higher crossbridge phosphorylation when compared with tissues without actin disruption. Shortening velocity, noise temperature, hysteresivity, and stiffness did not differ with and without actin disruption. These data suggest that actin disruption interferes with regulation of crossbridge cycling by crossbridge phosphorylation. Stiffness was linearly dependent on stress, suggesting that the force per attached crossbridge was not altered with force suppression or actin disruption. These data suggest a difference in the mechanical characteristics observed during force suppression and actin disruption, implying that force suppression does not mechanistically involve actin disruption. These data are most consistent with a model where force suppression involves the inhibition of phosphorylated crossbridge binding to thin filaments.
authors.affiliation: Box 800146, Cardiovascular Division, Univ. of Virginia Health System, Charlottesville, VA 22908-0146, USA. crembold@virginia.edu
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Rembold
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000199:Actins / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D017536:Carotid Artery, Common / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D050886:HSP20 Heat-Shock Proteins / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D018494:Histamine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010766:Phosphorylation; D013552:Swine; D053778:Thiazolidines / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D050886:HSP20 Heat-Shock Proteins; D018494:Histamine Agents; D053778:Thiazolidines; D005576:Colforsin; D006632:Histamine; C037067:latrunculin A