Previous studies concluding that the endogenous synthesis of NO is decreased in ADPKD used indirect methods of NO measurement, demonstrating that either endothelium-dependent relaxation in small resistance vessels or brachial artery flow-mediated dilatation was reduced [23, 49]; and/or that levels of serum/urinary NO metabolite, renal NOS protein/mRNA, and/or NOS activity were reduced [10, 11, 13, 15, 23]. Here, NOS2 is linked to autosomal dominant polycystic kidney disease.