New aspects of the renin-angiotensin system: angiotensin-converting enzyme 2 - a potential target for treatment of hypertension and diabetic nephropathy.

Batlle, Daniel; Soler, María José; Wysocki, Jan

PURPOSE OF REVIEW Whereas angiotensin-converting enzyme promotes the formation of angiotensin II, angiotensin-converting enzyme 2 promotes the degradation of angiotensin II to angiotensin-(1-7). We review recent studies dealing with angiotensin-converting enzyme 2 in kidney disease and hypertension, and discuss the potential therapeutic benefit of increasing angiotensin-converting enzyme 2 activity in the treatment of these diseases. RECENT FINDINGS In glomeruli from diabetic mice, angiotensin-converting enzyme 2 expression is downregulated, and pharmacological inhibition of angiotensin-converting enzyme 2 leads to worsening of albuminuria, increased mesangial matrix deposition and fibronectin expression. The deletion of the angiotensin-converting enzyme 2 gene in mice leads to worsening of angiotensin II-induced hypertension and has also been shown to cause glomerulosclerosis in aging male mice. SUMMARY Angiotensin-converting enzyme 2 is a key enzyme in the renin-angiotensin system that favors the degradation of angiotensin I and angiotensin II. Angiotensin-converting enzyme 2 inhibition by pharmacological means and by genetic deletion worsens kidney disease in diabetic mice. Strategies geared to increasing angiotensin-converting enzyme 2 activity may provide a novel therapeutic target within the renin-angiotensin system by enhancing angiotensin II degradation that may complement the current approach of inhibiting angiotensin II formation and action. Amplifying angiotensin-converting enzyme 2 activity may have a potential therapeutic role for kidney disease and hypertension.