Background: Vascular (interstitial) angiotensin (ANG) II production depends on circulating renin-angiotensin system (RAS) components. Mannose 6-phosphate (man-6-P) receptors and angiotensin II type 1 (AT1) receptors, via binding and internalization of (pro)renin and ANG II, respectively, could contribute to the transportation of these components across the endothelium. Objective: To investigate the mechanism(s) contributing to transendothelial RAS component transport. Methods: Human umbilical vein endothelial cells were cultured on transwell polycarbonate filters, and incubated with RAS components in the absence or presence of man-6-P, eprosartan or PD123319, to block man-6-P, AT1 and angiotensin II type 2 (AT2) receptors, respectively. Results: Apically applied (pro)renin and angiotensinogen slowly entered the basolateral compartment, in a similar manner as horseradish peroxidase, a molecule of comparable size that reaches the interstitium via diffusion only. Prorenin transport was unaffected by man-6-P. Apical ANG I and ANG II rapidly reached the basolateral fluid independent of AT1 and AT2 receptors. Basolateral ANG II during apical ANG I application was as high as apical ANG II, whereas during apical ANG II application it was lower. During basolateral ANG I application, ANG II generation occurred basolaterally only, in an angiotensin-converting enzyme (ACE)-dependent manner. Conclusions: Circulating (pro)renin, angiotensinogen, ANG I and ANG II enter the interstitium via diffusion, and interstitial ANG II generation is mediated, at least in part, by basolaterally located endothelial ACE.

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Keywords Angiotensin, Local renin-angiotensin system, Mannose 6-phosphate/insulin-like growth factor II receptor, Prorenin
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Journal Journal of Hypertension
van den Eijnden, M.M.E.D, de Bruin, R.J.A, de Wit, E.A, Sluiter, W.J, Deinum, J, Reudelhuber, T.L, & Danser, A.H.J. (2002). Transendothelial transport of renin-angiotensin system components. Journal of Hypertension, 20(10), 2029–2037. doi:10.1097/00004872-200210000-00023