Stimulation of cerebral and dermal microvascular endothelial cell proliferation by AT1 receptor antagonist losartan

Abstract

Aim: We have shown that cerebral angiogenesis is stimulated by chronic treatment of rats with the angiotensin II (ANG II) type 1 receptor (AT1R) antagonist, losartan (LOS). Because the trophic actions of ANG II via AT1R are well known, the finding that an AT1R antagonist increases angiogenesis is paradoxical. The aim is to determine whether cerebral (CMVEC) and dermal (DMVEC) microvascular endothelial cells differ in their growth responses to LOS treatment. Methods: Primary human CMVEC and DMVEC, passage 3–8, were seeded into 96-well plates (5000 cells/well) and allowed to adhere for 24 hrs. Cells were exposed to serum-free media (SFM) alone and in the presence of LOS (10 μM), ANG II (1 μM) or both for 48 hours. Cell density was quantified by a fluorescent dye proliferation assay at 480/520 nm. Results: Density of CMVEC increased with either ANG II stimulation (27.5%) or treatment with LOS, with (33.7%) or without ANG II (27.1%) compared to SFM alone. A similar but less robust pattern was seen with DMVEC with ANG II (8.9%), LOS + ANG II (15.2%) and LOS alone (19.0%). Conclusion: This suggests that CMVEC and DMVEC have similar proliferative responses so they do not appear to be tissue-specific. However, LOS alone has a similar effect to treatment with both the agonist and antagonist suggesting that LOS directly stimulates cell proliferation and that the effect is not due to receptor blockade per se. Supported by NIH HL29587 and HV28182