Angiotensin‐(1–7) stimulates angiogenesis in murine corpus cavernosum

Abstract

Angiotensin (Ang)‐(1–7), a metabolite of Angiotensin‐converting enzyme‐2 (ACE2), is cardiovascular protective. Recent studies have implicated an important role of angiogenic progenitor cells (APCs) in the functions of Ang‐(1–7). This study evaluated the effect of Ang‐(1–7) in the tissue angiogenesis independent of APCs. Strips of corpus cavernosum (CC) or aortic rings were isolated from mice and cultured in matrigel. Formation of sprouts and tubes by endothelial cells (EC) were evaluated. In some experiments, assays were performed in CC‐strips from mice following treatment with Ang‐(1–7) (100μg/Kg, s.c., 4 weeks). ECs from sinusoidal CC have migrated into the matrix in 24 to 48 hours, and endothelial sprouts and tubes were observed in 3–5 days. Ang‐(1–7) treatment potentiated this response that was lower than the effect of VEGF (100nM). Effect of Ang‐(1–7) was inhibited by Mas receptor antagonist A‐779, and was not affected by nitric oxide synthase blocker L‐NAME. CC strips from Ang‐(1–7)‐treated mice have shown increased sprout and tube formations compared to the control. In mouse aortic rings, angiogenesis was observed in 3 to 5 days and the migration of smooth muscle cells was seen by day 4. Treatment with Ang‐(1–7) has no effect. These studies support that Ang‐(1–7) stimulates angiogenesis without the involvement of APCs by activating Mas receptor in the sinusoids of CC and not in a conduit blood vessel.