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U. Walter, R. Waldmann, M. Nieberding, Intracellular mechanism of action of vasodilators, European Heart Journal, Volume 9, Issue suppl_H, June 1988, Pages 1–6, https://doi.org/10.1093/eurheartj/9.suppl_H.1
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Abstract
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, alpha1-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 A TPases.
- nitric oxide
- calcium channel blockers
- prostaglandins e
- blood platelets
- smooth muscle
- vasodilators
- calcium
- cyclic gmp
- muscle, smooth, vascular
- endothelium
- myosin light chains
- myosin light chain kinase
- nucleotides
- phosphatidylinositols
- phosphorylation
- protein kinase
- cyclic amp
- pharmacokinetics
- platelet aggregation
- nitroprusside sodium
- antagonists
- endothelium-dependent relaxing factors
- vasculature
- current good manufacturing practice
