Angiotensin II and gene expression in the kidney.
Angiotensin II, a potent vasoconstrictor, has a key role in renal injury and in the progression of chronic renal disease of diverse causes. In vascular smooth muscle cells, angiotensin II modulates growth, which may lead to hypertrophy and also may inhibit mitogen-stimulated DNA synthesis. The effects of angiotensin II on responsive cells are mediated by two classes of receptors, AT-1 and AT-2. Information obtained in the last decade indicates that angiotensin II increases the production of several autocrine factors, including transforming growth factor beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha), and platelet-derived growth factor A chain (PDGF). Angiotensin also increases the release of other growth factors such as endothelin, platelet-activating factor (PAF), and interleukin 6. In addition, it increases the "activity" of nuclear factor-kappaB (NF-kappaB) and the synthesis of angiotensinogen. The emerging picture indicates that the actions of angiotensin II may be related to factors that are released or upregulated by angiotensin II, possibly through NF-kappaB activation. It appears likely that many of the effects of angiotensin II on renal disease may be mediated by TGF-beta1, TNF-alpha, and changes in the activity of NF-kappaB. The use of ACE inhibitors or antagonists of AT-1 or AT-2 receptors in experimental animals decreases the levels of angiotensin II or limits its action, thereby interfering with the production and effects of the factors described.
Klahr
S
S
Department of Medicine and Cell Biology, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, MO 63110, USA. sklahr@imgate.wustl.edu
Morrissey
J
J
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology
D011945:Receptors, Angiotensin; D000804:Angiotensin II