High glucose (HG)‐induced angiotensin‐converting enzyme 2 (ACE2) and angiotensin (1–7) [Ang (1–7)] decrease is prevented by captopril, losartan and insulin in rat vascular smooth muscle cells (VSMCs)

Abstract

Ang (1–7) prevents the development of diabetic cardiovascular complications. In VSMCs ACE2 is a major source of Ang (1–7). ACE2 expression is PKCβII dependent and it is decreased by exposure to HG via Nox1‐derived superoxides. In diabetic animal models captopril and losartan restore circulating Ang (1–7) levels. This study was conducted to determine if in rat VSMCs these agents and insulin prevent HG‐induced ACE2 and Ang (1–7) decrease. Cells were maintained in normal glucose (NG) or HG (~4.1 mmol/l and ~23.1 mmol/l, accordingly) for up to 72 hours and exposed to captopril, losartan, insulin or angiotensin II (Ang II). The cell lysates were subjected to Western blot, RTQ‐PCR and Ang (1–7) radioimmunoassay. HG‐induced ACE2 and Ang (1–7) decrease was prevented by captopril, losartan and insulin. Ang II alone reduced ACE2 expression in the presence of NG, which was prevented by captopril and losartan, and partially by insulin. HG‐induced Nox1 increase was diminished by captopril, losartan and insulin, whereas Ang II‐induced Nox1 increase was reversed by captopril and losartan but not insulin. HG deceased PKCβII level that was blocked by captopril, losartan and insulin. These data suggest that these agents prevent HG‐induced ACE2 and Ang (1–7) decrease by diminishing HG‐induced Nox‐1 expression and by restoring PKCβII level in VSMCs (Supported by NIH grant 079109‐03 from the HLBI).