Mas Receptor Expression Research Articles

Reduction in renal ACE2 expression in subtotal nephrectomy in rats is ameliorated with ACE inhibition

Alterations within the RAS (renin–angiotensin system) are pivotal for the development of renal disease. ACE2 (angiotensin-converting enzyme 2) is expressed in the kidney and converts the vasoconstrictor AngII (angiotensin II) into Ang-(1–7), a peptide with vasodilatory and anti-fibrotic actions. Although the expression of ACE2 in the diabetic kidney has been well studied, little is known about its expression in non-diabetic renal disease. In the present study, we assessed ACE2 in rats with acute kidney injury induced by STNx (subtotal nephrectomy). STNx and Control rats received vehicle or ramipril (1 mg·kg−1 of body weight·day−1), and renal ACE, ACE2 and mas receptor gene and protein expression were measured 10 days later. STNx rats were characterized by polyuria, proteinuria, hypertension and elevated plasma ACE2 activity (all P<0.01) and plasma Ang-(1–7) (P<0.05) compared with Control rats. There was increased cortical ACE binding and medullary mas receptor expression (P<0.05), but reduced cortical and medullary ACE2 activity in the remnant kidney (P<0.05 and P<0.001 respectively) compared with Control rats. In STNx rats, ramipril reduced blood pressure (P<0.01), polyuria (P<0.05) and plasma ACE2 (P<0.01), increased plasma Ang-(1–7) (P<0.001), and inhibited renal ACE (P<0.001). Ramipril increased both cortical and medullary ACE2 activity (P<0.01), but reduced medullary mas receptor expression (P<0.05). In conclusion, our results show that ACE2 activity is reduced in kidney injury and that ACE inhibition produced beneficial effects in association with increased renal ACE2 activity. As ACE2 both degrades AngII and generates the vasodilator Ang-(1–7), a decrease in renal ACE2 activity, as observed in the present study, has the potential to contribute to the progression of kidney disease.

Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) levels in experimental biliary fibrosis

Background/AimsAngiotensin-converting enzyme 2 (ACE2), its product, angiotensin-(1–7) and its receptor, Mas, may moderate the adverse effects of angiotensin II in liver disease. We examined the expression of these novel components of the renin angiotensin system (RAS) and the production and vasoactive effects of angiotensin-(1–7) in the bile duct ligated (BDL) rat.MethodsBDL or sham-operated rats were sacrificed at 1, 2, 3 and 4 weeks. Tissue and blood were collected for gene expression, enzyme activity and peptide measurements. In situ perfused livers were used to assess angiotensin peptide production and their effects on portal resistance.ResultsHepatic ACE2 gene and activity (P < 0.0005), plasma angiotensin-(1–7) (P < 0.0005) and Mas receptor expression (P < 0.01) were increased following BDL compared to shams. Perfusion experiments confirmed that BDL livers produced increased angiotensin-(1–7) (P < 0.05) from angiotensin II and this was augmented (P < 0.01) by ACE inhibition. Whilst angiotensin II increased vasoconstriction in cirrhotic livers, angiotensin-(1–7) had no effect on portal resistance.ConclusionsRAS activation in chronic liver injury is associated with upregulation of ACE2, Mas and hepatic conversion of angiotensin II to angiotensin-(1–7) leading to increased circulating angiotensin-(1–7). These results support the presence of an ACE2-angiotensin-(1–7)-Mas axis in liver injury which may counteract the effects of angiotensin II.