Free radical production and angiotensin.
Angiotensin II (ANG II) has multiple effects on cardiovascular and renal cells, including vasoconstriction, cell growth, induction of proinflammatory cytokines, and profibrogenic actions. Recent studies provide evidence that ANG II could stimulate intracellular formation of reactive oxygen species (ROS) such as the superoxide anion (O2-). This ANG II-mediated ROS formation exhibits different kinetic and lower absolute concentrations than those traditionally observed during the respiratory burst of phagocytic cells, but it likely involves similar membrane-bound NAD(P)H-oxidases. Current evidence suggests that ANG II, through AT1-receptor activation, upregulates several subunits of this multienzyme complex, resulting in an increase in intracellular O2- concentration. ROS are involved in several signal pathways, and redox-sensitive transcriptional factors (AP-1, NF-kappaB) have been characterized. ANG II-induced ROS play a pivotal role in several pathophysiologic situations of vascular and renal cells such as hypertension, endothelial dysfunction, nitrate tolerance, atherosclerosis, and cellular remodeling. Although these perceptions suggest that drugs interfering with ANG II effects (ACE inhibitors, AT1 -receptor antagonist) may serve as antioxidants, preventing vascular and renal changes, the clinical studies are not so straightforward. In fact, only specific risk groups, such as patients with diabetes mellitus or renal insufficiency, may benefit from ACE inhibitors, whereas hard endpoints showed no advantage for ACE inhibitors in patients with essential hypertension.
Wolf
G
G
University of Hamburg, University Hospital Eppendorf, Department of Medicine, Division of Nephrology and Osteology, Pavilion 61, Martinistrasse 52, D-20246 Hamburg, Germany. WOLF@UKE.uni-hamburg.de
D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000502:physiology; D012307:Risk Factors; D015398:Signal Transduction; D015854:Up-Regulation
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D009569:Nitric Oxide; D019255:NADPH Oxidases