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.