NOS3 and endothelial dysfunction: Of note, aside from the canonical vasopressor effects via inducing the contraction of vascular smooth muscle cells, ang II also triggers endothelial dysfunction through downregulation of transient receptor potential vanilloid 4 (TRPV4), thereby sabotaging TRPV4-mediated calcium influx as well as the ensuing activation of eNOS and production of nitric oxide in endothelial cells (Kondapalli et al., 2023).