Regulation of angiotensin-converting enzyme 2 and Mas receptor by Ang-(1–7) in heart and kidney of spontaneously hypertensive rats

Inter-regulation between components of the renin-angiotensin system is common, but little is known about the direct regulatory effects of Ang-(1-7) on expression of tissue ACE2 and the Mas receptor. Eighteen male spontaneously hypertensive rats (SHR) and 20 normotensive Wistar-Kyoto rats were randomly allocated to four groups of 9-10 rats each and received either 24 µg/kg per hour of Ang-(1-7) in saline or saline alone (5 ml/h) by infusion for 14 consecutive days. Tail-cuff systolic blood pressures were recorded and ACE2 and Mas expression was measured using quantitative real-time PCR (QRT-PCR) and Western blotting. Cardiac and renal ACE2 mRNA was decreased in SHR. Although having no effects on blood pressure, Ang-(1-7) down-regulated cardiac ACE2 mRNA in normotensive rats (1.80 ± 0.27 vs. 5.89 ± 0.62, p < 0.05) but did not change renal ACE2. Ang(1-7) down-regulated cardiac Mas mRNA of Wistar rats only (2.50 ± 0.44 vs. 8.10 ± 1.33, p < 0.05), and renal Mas mRNA of SHR receiving Ang-(1-7) was decreased (0.44 ± 0.09 vs. 1.00 ± 0.17, p < 0.05). Results from Western blot tests were consistent with those from QRT-PCR tests. These results suggest organ-specific regulation of local ACE2 and Mas expression by continuous infusion of Ang-(1-7) which did not alter blood pressure of either SHR or Wistar rats.