Angiotensin II receptor antagonists and the kidney

The kidney is not only the source of circulating renin, which determines the plasma concentration of angiotensin II, but it is also one of the main targets of angiotensin II. Thus, angiotensin II exerts an important physiologic influence on renal function through its ability to modulate renal hemodynamics as well as glomerular and tubular functions. Moreover, angiotensin II appears to contribute to the progressive deterioration of renal function commonly observed in renal diseases. The availability of new orally active, nonpeptide angiotensin II receptor antagonists lacking agonistic or kinin- and prostaglandin-inducing properties has offered the possibility of investigating further the renal influence of angiotensin II. Thus, it is now clear that most if not all renal effects of angiotensin II are mediated by the activation of AT1 receptors, although the AT2 subtype is present in the kidney. Furthermore, increasing experimental evidence indicates that the long-term renal protective effect of angiotensin-converting enzyme inhibitors is indeed due to the inhibition of the renin-angiotensin system rather than to the activation of non-angiotensin II mechanisms.