NOS3 and chronic kidney disease: Based on experimental studies investigating the role of CKD-induced cardiac oxidative/nitrative stress, the over-activation of NADPH-oxidase (Goux et al., 2011; Suematsu et al., 2018), especially its NOX4 (Bai et al., 2009; Fukunaga et al., 2012; Kuczmarski et al., 2014; Han et al., 2015; Liu et al., 2015) and NOX2 isoforms (Yin et al., 2016), uncoupled eNOS and iNOS (Chang et al., 2015; Oosterhuis et al., 2017) are the main sources of increased cardiac ROS/RNS production in T4CRS.