Intracellular mechanism of action of vasodilators.
Intracellular mechanism of action of vasodilators.
复制标题
血管扩张剂的细胞内作用机制。
DOI：
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发表时间：
1988
影响因子：
39.3
通讯作者：
M. Nieberding
中科院分区：
文献类型：
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作者：
U. Walter;R. Waldmann;M. Nieberding
直接作用于血管系统水平的血管扩张剂可分为内皮依赖性或非内皮依赖性。内皮依赖性药物刺激内皮细胞产生内皮衍生的松弛因子(新近被发现为NO)，从而松弛血管平滑肌，增加cGMP。非内皮依赖性血管扩张剂可分为钙拮抗剂、α1-肾上腺素能拮抗剂、cAMP升高剂和cGMP升高剂。人们普遍认为，肌球蛋白轻链的钙依赖磷酸化启动了平滑肌收缩。大量证据表明，某些血管扩张剂通过激活cAMP和cGMP依赖的蛋白磷酸化来抑制钙依赖的肌球蛋白轻链的磷酸化和平滑肌的收缩。由于血管平滑肌细胞和血小板有许多共同的性质，由于cAMP和cGMP升高的血管扩张剂既抑制血管收缩又抑制血小板聚集，因此我们以人血小板为研究对象来研究血管扩张剂对蛋白质磷酸化的影响。结果表明，cAMP和cGMP调节的蛋白激酶分别是前列腺素E_1和硝普钠诱导的蛋白磷酸化的细胞内介质。此外，前列腺素E1和硝普钠刺激的蛋白质磷酸化被发现与抑制磷脂酰肌醇循环有关。环核苷酸升高型血管扩张剂可能通过调节磷脂酰肌醇循环的流量、肌球蛋白轻链激酶和钙ATPase的活性来抑制平滑肌收缩和血小板聚集。
Vasodilators that act directly at the level of the vasculature may be classified as either endothelium-dependent or endothelium-independent agents. Endothelium-dependent agents stimulate the endothelium to produce endothelium-derived relaxing factor (recently identified as NO) which relaxes vascular smooth muscle and increases cGMP. Endothelium-independent vasodilators may be divided into calcium antagonists, alpha 1-adrenergic antagonists, cAMP-elevating agents and cGMP-elevating agents. It is generally accepted that calcium-dependent phosphorylation of myosin light chains initiates smooth muscle contraction. A variety of evidence suggests that certain vasodilators inhibit calcium-dependent phosphorylation of myosin light chains and smooth muscle contraction via activation of cAMP- and cGMP-dependent protein phosphorylation. Since vascular smooth muscle cells and platelets have many properties in common, and since cAMP- and cGMP-elevating vasodilators inhibit both smooth muscle contraction and platelet aggregation, human platelets were used to study the effects of vasodilators on protein phosphorylation. It could be demonstrated that cAMP- and cGMP-regulated protein kinases are the intracellular mediators for prostaglandin-E1- and nitroprusside-induced protein phosphorylation, respectively. Furthermore, prostaglandin-E1- and nitroprusside-stimulated protein phosphorylation was found to be associated with an inhibition of the phosphatidylinositol cycle. Cyclic nucleotide-elevating vasodilators may inhibit smooth muscle contraction and platelet aggregation by regulating the flux through the phosphatidylinositol cycle, and the activity of myosin light-chain kinase and of calcium ATPases.