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2016 ; 11
(5
): e0154460
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English Wikipedia
Papaverine Prevents Vasospasm by Regulation of Myosin Light Chain Phosphorylation
and Actin Polymerization in Human Saphenous Vein
#MMPMID27136356
Hocking KM
; Putumbaka G
; Wise ES
; Cheung-Flynn J
; Brophy CM
; Komalavilas P
PLoS One
2016[]; 11
(5
): e0154460
PMID27136356
show ga
OBJECTIVE: 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. APPROACH AND RESULTS: HSV was
equilibrated in a muscle bath, pre-treated with 1 mM papaverine followed by 5 ?M
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. CONCLUSIONS: 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.