Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases.
A growing body of evidence supports the notion that angiotensin II (Ang II), the central product of the renin-angiotensin system, may play a central role not only in the etiology of hypertension but also in the pathophysiology of cardiovascular and renal diseases in humans. In this review, we focus on the role of Ang II in cardiovascular and renal diseases at the molecular and cellular levels and discuss up-to-date evidence concerning the in vitro and in vivo actions of Ang II and the pharmacological effects of angiotensin receptor antagonists in comparison with angiotensin-converting enzyme inhibitors. Ang II, via AT(1) receptor, directly causes cellular phenotypic changes and cell growth, regulates the gene expression of various bioactive substances (vasoactive hormones, growth factors, extracellular matrix components, cytokines, etc.), and activates multiple intracellular signaling cascades (mitogen-activated protein kinase cascades, tyrosine kinases, various transcription factors, etc.) in cardiac myocytes and fibroblasts, vascular endothelial and smooth muscle cells, and renal mesangial cells. These actions are supposed to participate in the pathophysiology of cardiac hypertrophy and remodeling, heart failure, vascular thickening, atherosclerosis, and glomerulosclerosis. Furthermore, in vivo recent evidence suggest that the activation of mitogen-activated protein kinases and activator protein-1 by Ang II may play the key role in cardiovascular and renal diseases. However, there are still unresolved questions and controversies on the mechanism of Ang II-mediated cardiovascular and renal diseases.
Kim
S
S
Department of Pharmacology, Osaka City University Medical School, Abeno-ku, Osaka, Japan. kims@med.osaka-cu.ac.jp
Iwao
H
H
D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D002318:Cardiovascular Diseases / Q000473:pathology / Q000503:physiopathology*; D006321:Heart / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000502:physiology; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology*; D011945:Receptors, Angiotensin / Q000145:classification / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D000804:Angiotensin II