Interplay between calcium and reactive Oxygen/Nitrogen species: An essential paradigm for vascular smooth muscle signaling

Signaling cascades initiated or regulated by calcium (Ca²⁺), reactive oxygen (ROS), and nitrogen (RNS) species are essential to diverse physiological and pathological processes in vascular smooth muscle. Stimuli-induced changes in intracellular Ca²⁺ regulate the activity of primary ROS and RNS, producing enzymes including NADPH oxidases (Nox) and nitric oxide synthases (NOS). At the same time, alteration in intracellular ROS and RNS production reciprocates through redox-based post-translational modifications altering Ca²⁺ signaling networks. These may include Ca²⁺ pumps such as sarcoplasmic endoplasmic reticulum Ca ²⁺-ATPase (SERCA), voltage-gated channels, transient receptor potential canonical (TRPC), melastatin2 (TRPM2), and ankyrin1 (TRPA1) channels, store operated Ca²⁺ channels such as Orai1/stromal interaction molecule 1 (STIM1), and Ca²⁺ effectors such as Ca²⁺/ calmodulin-dependent protein kinase II (CaMKII). In this review, we summarize and highlight current experimental evidence supporting the idea that cross-talk between Ca²⁺ and ROS/RNS may represent a well-integrated signaling network in vascular smooth muscle. Antioxid.