Angiotensin converting enzyme 2 in the kidney

Abstract

1. Angiotensin converting enzyme 2 (ACE2) is an important homeostatic component of the renin angiotensin system (RAS). ACE2 both degrades the vasoconstrictor, angiotensin II and generates the potent vasodilator peptide, angiotensin 1-7. These actions counterbalance those of ACE. 2. ACE2 is highly expressed in the healthy kidney, particularly in the proximal tubules, where it colocalizes with ACE and angiotensin receptors. 3. Kidney disease and subtotal nephrectomy is associated with a reduction in renal ACE2 expression, possibly facilitating the damaging effects of angiotensin II in the failing kidney. Acquired or genetic ACE2 deficiency also appears to exacerbate renal damage and albuminuria in experimental models, supporting this hypothesis. 4. ACE2 also has an important role in blood pressure control. Many models of hypertension are associated with reduced ACE2 expression. Although ACE2 KO animals are normotensive, in states associated with activation of the RAS, ACE2 overexpression improves blood pressure control and reduces angiotensin responsiveness.

Figure 1

Schematic representation of the proteolytic components of the renin–angiotensin system. ACE, angiotensin converting enzyme; ACE2, angiotensin converting enzyme 2; NEP, neutral endopeptidase‐24.11; PEP, prolyl endopeptidase.

Figure 2

The renal expression of angiotensin converting enzyme 2 (ACE2) in cortical sections from control (a) is modified following the induction of experimental diabetes in male C57Bl6 mice (b). Original magnification ×40.

Figure 3

Expression of angiotensin converting enzyme (ACE) and ACE2 gene as measured by real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) in cortical homogenates from control and diabetic (1 and 32 weeks) Sprague‐Dawley rats. Data are shown as mean percentage control ± SEM; *P < 0.05 versus control.

Figure 4

Gene expression of angiotensin converting enzyme (ACE) and ACE2 gene as measured by real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) in cortical homogenates from control (cnt) and 12‐week subtotal nephrectomized (stnx) Sprague Dawley rats. Data are shown as mean percentage control ± SEM, *P < 0.05 versus control.