ANGIOTENSIN-II AND GENE-EXPRESSION IN THE KIDNEY

Angiotensin II, a potent vasoconstrictor, has a key role in renal inju ry and in the progression of chronic renal disease of diverse causes, In vascular smooth muscle cells, angiotensin II modulates growth, whic h may lead to hypertrophy and also may inhibit mitogen-stimulated DNA synthesis. The effects of angiotensin II on responsive cells are media ted by two classes of receptors, AT-1 and AT-2. Information obtained i n the last decade indicates that angiotensin II increases the producti on of several autocrine factors, including transforming growth factor beta 1 (TGF-beta 1), tumor necrosis factor-alpha (TNF-alpha), and plat elet-derived growth factor A chain (PDGF), Angiotensin also increases the release of other growth factors such as endothelin, platelet-activ ating factor (PAF), and interleukin 6. In addition, it increases the ' 'activity'' of nuclear factor-kappa B (NF-kappa B) and the synthesis o f angiotensinogen. The emerging picture indicates that the actions of angiotensin II may be related to factors that are released or upregula ted by angiotensin II, possibly through NF-kappa B activation. It appe ars likely that many of the effects of angiotensin II on renal disease may be mediated by TGF-beta 1, TNF-alpha, and changes in the activity of NF-kappa B. The use of ACE inhibitors or antagonists of AT-1 or AT -2 receptors in experimental animals decreases the levels of angiotens in II or limits its action, thereby interfering with the production an d effects of the factors described, (C) 1998 by the National Kidney Fo undation, Inc.