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S. Nilsson, L. Geng, K. Persson; Angiotensin (1–7) Inhibits DNA Synthesis in Vascular Smooth Muscle Cells (VSMC) From Porcine Ciliary Arteries . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3896.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Vascular factors are thought to be involved in the pathogenesis of several ocular diseases, and the interest has been especially focused on the renin–angiotensin system (RAS). Angiotensin II (Ang II), which causes hypertension and proliferation of VSMC, has been considered the key mediator in RAS. However, angiotensin 1–7 (Ang(1–7)), which is formed from Ang II by the action of angiotensin converting enzyme 2, acts as a physiological antagonist to Ang II, causing hypotension and inhibition of proliferation. The aim of the present study was to investigate the effect of Ang(1–7) on the growth of VSMC from ciliary arteries. Methods: Cultures of VSMC were obtained from explants of porcine ciliary arteries. At confluence, the cells were harvested and seeded on 96–well plates. After the cells had been made quiescent, they were stimulated by 1% serum during 24 hours. The incorporation of 3[H]–thymidine was used to measure DNA synthesis, in the absence and presence of Ang(1–7). The following agents were tested for their ability to block the effect of Ang(1–7): [Sar1, Val5, Ala8]AngII (non–selective AT receptor antagonist), [Sar1,Ile8]AngII (selective AT1 receptor antagonist), D–Pro7–Ang(1–7) (Ang(1–7) receptor antagonist), Hoe 140 (bradykinin B2 receptor antagonist), 1400W (selective inhibitor of iNOS) and L–NMMA (non–selective NOS inhibitor). Results: Ang(1–7) caused a concentration dependent decrease in 3[H]–thymidine incorporation, with maximal effect (–35±9%;P≤0.05) at 10–7 M. The decrease in 3[H]–thymidine incorporation caused by Ang(1–7) was completely reversed by10–7 M of D–Pro7–Ang(1–7), by 10–6M of [Sar1, Val5, Ala8]AngII or Hoe 140, and by 10–5 M of 1400W or L–NMMA. Conclusions: In accord with previous studies, using VSMC from large arteries, Ang(1–7) inhibited the proliferation of VSMC from ciliary arteries. No definitive conclusion can be made concerning the type of receptor that is activated by Ang(1–7), but its activation leads to increased formation of nitric oxide. The opposing actions of Ang II and Ang(1–7) indicate that the possible involvement of RAS in ocular pathology may be more complex than previously thought.
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