The intrarenal renin-angiotensin system: does it exist? Implications from a recent study in renal angiotensin-converting enzyme knockout mice.

A large body of evidence supports the presence of local production of angiotensins in the kidney. It is widely believed that renin-angiotensin system (RAS) blockers, through interference with such production and/or the local effects of angiotensin (Ang) II, exert protective renal effects. Yet, whether such production affects blood pressure independently from the circulating RAS is still a matter of debate. To investigate this, a recent study by Gonzalez-Villalobos et al. (J Clin Invest 2013; 123: 2011-2023) has studied the consequences of infusing Ang II or the nitric oxide synthase inhibitor l-NAME in mice lacking renal angiotensin-converting enzyme (ACE). They observed blunted blood pressure and renal responses in the renal ACE knockout mice versus wild-type controls. This review discusses to what degree these findings can be considered as unequivocal evidence for ACE-mediated Ang II formation in the kidney as an independent determinant of hypertension.