title: Papaverine Prevents Vasospasm by Regulation of Myosin Light Chain Phosphorylation and Actin Polymerization in Human Saphenous Vein.
abstract: Papaverine is used to prevent vasospasm in human saphenous veins (HSV) during vein graft preparation prior to implantation as a bypass conduit. Papaverine is a nonspecific inhibitor of phosphodiesterases, leading to increases in both intracellular cGMP and cAMP. We hypothesized that papaverine reduces force by decreasing intracellular calcium concentrations ([Ca2+]i) and myosin light chain phosphorylation, and increasing actin depolymerization via regulation of actin regulatory protein phosphorylation.
  
  
  
  HSV was equilibrated in a muscle bath, pre-treated with 1 mM papaverine followed by 5 μM norepinephrine, and force along with [Ca2+]i levels were concurrently measured. Filamentous actin (F-actin) level was measured by an in vitro actin assay. Tissue was snap frozen to measure myosin light chain and actin regulatory protein phosphorylation. Pre-treatment with papaverine completely inhibited norepinephrine-induced force generation, blocked increases in [Ca2+]i and led to a decrease in the phosphorylation of myosin light chain. Papaverine pre-treatment also led to increased phosphorylation of the heat shock-related protein 20 (HSPB6) and the vasodilator stimulated phosphoprotein (VASP), as well as decreased filamentous actin (F-actin) levels suggesting depolymerization of actin.
  
  
  
  These results suggest that papaverine-induced force inhibition of HSV involves [Ca2+]i-mediated inhibition of myosin light chain phosphorylation and actin regulatory protein phosphorylation-mediated actin depolymerization. Thus, papaverine induces sustained inhibition of contraction of HSV by the modulation of both myosin cross-bridge formation and actin cytoskeletal dynamics and is a pharmacological alternative to high pressure distention to prevent vasospasm.
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Hocking
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Gowthami
authors.initials: G
authors.lastname: Putumbaka
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Wise
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Joyce
authors.initials: J
authors.lastname: Cheung-Flynn
authors.affiliation: VA Tennessee Valley Healthcare System, Nashville, Tennessee, United States of America.|Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Brophy
authors.affiliation: VA Tennessee Valley Healthcare System, Nashville, Tennessee, United States of America.|Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Padmini
authors.initials: P
authors.lastname: Komalavilas
mesh_terms: D000199:Actins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism*; D010208:Papaverine / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012501:Saphenous Vein / Q000187:drug effects* / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D000199:Actins; D018994:Myosin Light Chains; D010208:Papaverine; D002118:Calcium