Abstract
Signaling cascades initiated or regulated by calcium (Ca(2+)), reactive oxygen (ROS), and nitrogen (RNS) species are essential to diverse physiological and pathological processes in vascular smooth muscle. Stimuli-induced changes in intracellular Ca(2+) 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 Ca(2+) signaling networks. These may include Ca(2+) 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 Ca(2+) channels such as Orai1/stromal interaction molecule 1 (STIM1), and Ca(2+) effectors such as Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). In this review, we summarize and highlight current experimental evidence supporting the idea that cross-talk between Ca(2+) and ROS/RNS may represent a well-integrated signaling network in vascular smooth muscle.