REN and endothelial dysfunction: Hyperuricaemia can for example induce high BP through activation of the renin–angiotensin system, either directly by decreasing neuronal nitric oxide synthesis in the juxtaglomerular apparatus or indirectly through reduced renal perfusion due to the induction of cyclooxygenase-2 in the macula densa and arterioles [15, 16], and might contribute to endothelial dysfunction, as noted by a reduction in nitric oxide metabolites [23].