Mechanisms of progressive renal disease: role of angiotensin II, cyclooxygenase products and nitric oxide.
There is mounting evidence that a number of inflammatory mechanisms play a crucial role in the pathogenesis of both immune- and non-immune-mediated glomerulopathies. These mechanisms include T lymphocyte activation, macrophage infiltration and the expression of several cytokines, growth factors and adhesion molecules. Inflammation may also be strongly influenced by three, until recently, unsuspected mediators: angiotensin II, cyclooxygenase derivatives and nitric oxide. Angiotensin II exerts several biological actions that are completely unrelated to its well-known haemodynamic effects, and can mediate cell proliferation, renal fibrosis and the synthesis of other proinflammatory compounds. Cyclooxygenase products have been long associated with non-renal inflammatory phenomena such as arthritis, and could mediate several steps of chronic renal inflammation. Although nitric oxide is generally regarded as a physiological vasodilator with irreplaceable homeostatic effects, it is possible that it participates in the pathogenesis of progressive nephropathies. Treatment with antagonists of these three compounds, alone or in combination, may represent a valuable therapeutic tool in the struggle to arrest or attenuate progressive renal disease.
Zatz
Roberto
R
Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. rzatz@usp.br
Fujihara
Clarice Kazue
CK
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology; D005920:Glomerular Mesangium / Q000166:cytology; D006801:Humans; D007249:Inflammation / Q000150:complications; D007674:Kidney Diseases / Q000209:etiology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D012083:Renin / Q000502:physiology
D000804:Angiotensin II; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin