Angiotensin (1‐7) formation in angiotensin converting enzyme 2 knockout mice

Abstract

Angiotensin converting enzyme 2 (ACE2) and its product, angiotensin (1‐7) (Ang (1‐7)), have been shown to protect against renal and cardiovascular dysfunction in animal models of diabetes and hypertension. We found that under baseline conditions, deletion of ACE2 results in a normal mouse phenotype with little or no change in blood pressure and albumin/creatinine excretion in 16 wks old ACE2 knockout (KO) mice compared to wild type (WT) mice. In addition, urinary and renal Ang (1‐7) were not changed suggesting that other factors regulate loss of ACE2. Presence of other peptidases known to form Ang (1‐7), neprilysin (NEP) and angiotensin converting enzyme (ACE), was affirmed using western blot in ACE2KO and WT mice. Activity of NEP and ACE in ACE2KO and WT kidney homogenates was analyzed by mass spectrometry. Results indicate that other proteolytic pathways may be involved in the enzymatic cascade producing Ang (1‐7) thus compensating for ACE2 deficiency. Elucidation of ACE2 independent Ang (1‐7) formation may have clinical implications for treatment of cardiovascular and renal dysfunction. Supported by NIH R01HL093567 and AHA 10PRE4330004 (NMW).