Angiotensin II and oxidized LDL: an unholy alliance creating oxidative stress

Reactive oxygen species are produced continuously in many, not only vascular or renal, tissues and are part of the unspecific defence system. However, in various vascular or renal diseases enhanced formation of reactive oxygen species is thought to be pathogenic, e.g. in atherosclerosis, glomerular disease, renal failure, pyelonephritis or aminoglycoside nephropathy [1–4]. In the vascular system, the formation of O2− from endothelial cells, smooth muscle cells and macrophages seems to be of major relevance [3] mainly due to its reaction with nitric oxide (NO), particularly in the setting of hypercholesterolaemia and atherosclerosis [5]. NO, the most important endothelium-derived relaxing factor, is scavenged by O2− [6,7]. NO reacts with O2− to yield peroxynitrite (ONOO−), which is rather stable but can rearrange to form nitrate and the highly reactive OH• radical. Important pathophysiological consequences of enhanced oxygen radical formation for the vascular system are: (i) attenuation of the endothelium-dependent dilation, resulting in disturbed organ perfusion and systemic hypertension [8]; (ii) production of OH• radicals, which cause cellular damage and may contribute to inflammation [9]; and (iii) induction of apoptosis [10,11]. In the kidneys, O2− production has been detected in vascular cells, juxtaglomerular cells, tubular cells, podocytes, mesangial cells and isolated glomeruli. One example of a renal disease where enhanced formation of reactive oxygen species may play a causal role is membranous nephropathy [12]. In passive Heymann nephritis (PHN), an experimental form of membranous nephropathy, it was demonstrated that H2O2 is formed and leads to glomerular damage [13]. Other important consequences of enhanced oxidative stress for renal function are stimulation of renin release from juxtaglomerular cells, glomerular injury, stimulation of mesangial cell growth and hypertrophy of tubular epithelial cells [4,14–16].