Flow-mediated vasodilation through mechanosensitive G protein-coupled receptors in endothelial cells.

Currently, endothelium-dependent vasodilatation involves three main mechanisms: production of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS), synthesis of prostanoids by cyclooxygenase, and/or opening of calcium-sensitive potassium channels. Researchers have proposed multiple mechanosensors that may be involved in flow-mediated vasodilation (FMD), including G protein-coupled receptors (GPCRs), ion channels, and intercellular junction proteins, among others. However, GPCRs are considered the major mechanosensors that play a pivotal role in shear stress signal transduction. Among mechanosensitive GPCRs, G protein-coupled receptor 68, histamine H1 receptors, sphingosine-1-phosphate receptor 1, and bradykinin B2 receptors have been identified as endothelial sensors of flow shear stress regulating flow-mediated vasodilation. Thus, this review aims to expound on the mechanism whereby flow shear stress promotes vasodilation through the proposed mechanosensitive GPCRs in ECs.