Vesnarinone is a novel synthetic inotropic agent. Recently, it has been reported that
vesnarinone inhibits
adenosine uptake in the B-lymphocytoid cell line. Since extracellular
adenosine is cardioprotective, we examined whether
vesnarinone inhibits
adenosine uptake in cells constituting the cardiovascular system. 1 microCi of -3H-adenosine was added to cells of the myocyte cell line (C2C12), human coronary smooth muscle cell line (HCASMC), human and bovine coronary endothelial cell lines (HCAEC and BCAEC), bovine arterial endothelial cell line (BAEC), and human umbilical venous endothelial cell line (HUVEC). After 10 s-5 min, cells were separated from free [3H]
adenosine, and the radioactivity was measured. When 0.1-100 microM of
vesnarinone was added to each cell line, the uptake of
adenosine was inhibited dose-dependently {% inhibition of -3H-adenosine uptake
at 10 and 30 microM of
vesnarinone: 14 and 33% (C2C12), 47 and 72% (HCASMC), 37 and 58% (HCAEC), 42 and 68% (BCAEC), 19 and 68% (BAEC), 29 and 59% (HUVEC)}. The cellular viability of HCAEC exposed to 60 min of
hypoxia and 60 min of reoxygenation increased from 34+/-5 to 67+/-6% (
Trypan blue exclusion test) and 23+/-5 to 78+/-6% (LDH release), which was completely blunted by
8-sulfophenyltheophylline, an
adenosine receptor antagonist, and was partially blunted by
alpha,beta-methyleneadenosine 5'-diphosphate, an inhibitor of
ecto-5'-nucleotidase. We also found that
vesnarinone is cytoprotective against
hypoxia and reoxygenation in C2C12 and HCASMC. We conclude that
vesnarinone inhibits the uptake of
adenosine in cardiovascular cells, which contributes to cytoprotection.