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David Arredondo, Edith Arnold, Celina Garcia, Gonzalo Martinez de la Escalera, Carmen Clapp, Stephanie Thebault; Vasoinhibins Reduce The Bradykinin-induced Increase Of Endothelial Permeability In Vitro And In Vivo. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4889.
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Vasoinhibins are proteolytically derived fragments of the hormone prolactin that prevent the excessive retinal vasopermeability (RVP) associated with diabetes (JCI 118:2291, 2008). Bradykinin (BK) also contributes to the RVP increase in diabetes. Here, we investigated whether vasoinhibins attenuate the increase of both endothelial cell monolayer permeability and RVP stimulated by BK.
The paracellular permeability of bovine umbilical vein endothelial cell (BUVEC) monolayers cultured on permeable transwell filters was measured by assaying horse-radish peroxidase (HRP) flux. BK (10 µM) alone or combined with vasoinhibins (10 nM) was added to the upper filter compartment. The contribution of nitric oxide (NO) production was evaluated using the NO donor DETANONO-ate or the NO synthesis inhibitor L-NAME. RVP was quantified by the Evans blue method. Changes in retinal microvasculature diameter were observed by staining blood vessels in flat-mounted retina from male Wistar rats intravitreously injected with BK (60 pg) alone or in combination with vasoinhibins (1 µg).
Vasoinhibins prevented the BK-induced increase of BUVEC permeability, and L-NAME had a similar effect, whereas DETANONO-ate reversed the vasoinhibin action. Moreover, the intravitreal injection of BK increased both RVP and retinal microvasculature diameter, and these effects were prevented when BK was co-injected with vasoinhibins.
Vasoinhibins reduce the BK-induced increase of paracellular permeability in endothelial monolayers through the NO pathway. Also, vasoinhibins prevent the BK-induced increase of RVP and retinal vasodilation. Our findings support the protective role of vasoinhibins in diabetic macular edema.
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