title: The intrarenal renin-angiotensin system: does it exist? Implications from a recent study in renal angiotensin-converting enzyme knockout mice.
abstract: 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.
authors.affiliation: Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Lu
authors.forename: Lodi C W
authors.initials: LC
authors.lastname: Roksnoer
authors.forename: Alexander H Jan
authors.initials: AH
authors.lastname: Danser
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A
keywords: ACE inhibitor; angiotensin; chymase; diabetes; hypertension; renin