Angiotensin II:: a key factor in the inflammatory and fibrotic response in kidney diseases

Angiotensin II (AngII) participates in the pathogenesis of renal diseases, through the regulation of two key processes inflammation and fibrosis. AT(1) and AT(2) are the main receptors of AngII. AT(1) mediates most of the actions of AngII. This receptor regulates the expression of profibrotic factors, such as connective tissue growth factor (CTGF). The Smad signalling pathway and the Rho/Rho kinase system are two novel mechanisms involved in AngII-induced matrix regulation recently described. The role of AT(2) receptors in renal pathophysiological processes is not fully elucidated. Experimental data suggest that AT(2) receptors through activation of nuclear factor-kappa B participate in renal inflammatory cell recruitment. Studies in animal models of kidney injury have shown that the combined blockade of both AT(1) and AT(2) receptors, as well as the inhibition of the NF-kappa B pathway are necessary to stop the inflammatory process fully. On the whole, these data highlight the complex signalling systems activated by AngII and suggest novel potential targets to block fibrosis and inflammation in renal diseases.