Fox A A, Borchard U, Neumann M
J Cardiovasc Pharmacol. 1983 Mar-Apr;5(2):309-16. doi: 10.1097/00005344-198303000-00024.
Vanadate is a potent inhibitor of Na+,K+-ATPase derived from bovine aorta. The Ca2+, Mg2+-ATPase of the same preparation was inhibited at 10 times higher concentrations. Compared with [3H]ouabain, 48V bound quickly to bovine aortic microsomes. Equilibrium binding experiments revealed one high-affinity, low-capacity and one low-affinity binding site for 48V, whereas [3H]ouabain possessed only one binding site of high affinity. A high NADH-vanadate reductase activity was measured in the same preparation, suggesting that, in this tissue, vanadate may be converted to vanadyl, a form to which the Na+,K+-ATPase is relatively insensitive. An increase in the contractile force of isolated rabbit aorta was measured with the following potency: phenylephrine greater than ouabain greater than vanadate. The order in intrinsic activity was as follows: phenylephrine congruent to ouabain greater than vanadate. The action of vanadate was rapid in onset and stable over several hours, while that of ouabain was slow and transitory. Vanadate increased tension in isolated rabbit veins to an extent similar to phenylephrine, but at concentrations two orders of magnitude higher. Vanadate action decreased with decreasing (Ca2+)0, but remained constant at a constant ratio of (Ca2+)0/(Na+)2(0). Vanadate-induced increases in tension were decreased by verapamil by about 43% and persisted in a solution in which Na+ was replaced by Li+. Vanadate increased electrically stimulated contractions. It is concluded that most of the effect of vanadate is due to an increase in calcium influx into the smooth muscle cell and that the effect of vanadate on Na+,Ca2+ exchange is of minor importance.
钒酸盐是一种源自牛主动脉的Na⁺,K⁺-ATP酶的强效抑制剂。同一制剂中的Ca²⁺,Mg²⁺-ATP酶在浓度高10倍时受到抑制。与[³H]哇巴因相比，⁴⁸V能快速结合到牛主动脉微粒体上。平衡结合实验显示⁴⁸V有一个高亲和力、低容量结合位点和一个低亲和力结合位点，而[³H]哇巴因只有一个高亲和力结合位点。在同一制剂中检测到高NADH-钒酸盐还原酶活性，这表明在该组织中，钒酸盐可能转化为钒离子，而Na⁺,K⁺-ATP酶对这种形式相对不敏感。测量了离体兔主动脉收缩力的增加，其效力顺序如下：去氧肾上腺素＞哇巴因＞钒酸盐。内在活性顺序如下：去氧肾上腺素≈哇巴因＞钒酸盐。钒酸盐的作用起效迅速且在数小时内稳定，而哇巴因的作用缓慢且短暂。钒酸盐使离体兔静脉张力增加的程度与去氧肾上腺素相似，但浓度高两个数量级。钒酸盐的作用随（Ca²⁺）₀降低而减弱，但在（Ca²⁺）₀/（Na⁺）₂₀保持恒定的比例下保持不变。维拉帕米使钒酸盐诱导的张力增加降低约43%，并且在Na⁺被Li⁺取代的溶液中仍持续存在。钒酸盐增加电刺激收缩。结论是钒酸盐的大部分作用是由于平滑肌细胞钙内流增加，并且钒酸盐对Na⁺,Ca²⁺交换的作用不太重要。
