Jonnelle M. Edwards, Cameron G. McCarthy and Camilla F. Wenceslau* Pages 3723 - 3732 ( 10 )
The endothelium produces many substances that can regulate vascular tone. Acetylcholine is a widely used pharmacological tool to assess endothelial function. In general, acetylcholine binds to G-protein coupled muscarinic receptors that mediate a transient elevation in intracellular, free calcium. This intracellular rise in calcium is responsible for triggering several cellular responses, including the synthesis of nitric oxide, endothelium- derived hyperpolarizing factor, and eicosanoids derived from arachidonic acid. Endothelial arachidonic acid metabolism is also an important signaling pathway for mediating inflammation. Therefore, in conditions with sustained and excessive inflammation such as hypertension, arachidonic acid serves as a substrate for the synthesis of several vasoconstrictive metabolites, predominantly via the cyclooxygenase and lipoxygenase enzymes. Cyclooxygenase and lipoxygenase products can then activate G-protein coupled receptors expressed on vascular smooth muscle cells to causes contractile responses. As a result, acetylcholine-induced contraction due to arachidonic acid is a commonly observed feature of endothelial dysfunction and vascular inflammation in hypertension. In this review, we will critically analyze the literature supporting this concept, as well as address the potential underlying mechanisms, including the possibility that arachidonic acid signaling is diverted away from the synthesis of pro-resolving metabolites in conditions such as hypertension.
Endothelium, arachidonic acid metabolites, vascular function, acetylcholine, hypertension, G-protein.
Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine & Life Sciences, Toledo, OH, Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine & Life Sciences, Toledo, OH, Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine & Life Sciences, Toledo, OH