VEGF activation of VEGFR2 initiates several downstream signalling cascades leading to adherens protein internalisation, calcium release, and stress fiber formation. Thrombin and histamine, via G-protein coupled receptors, results in RhoA activation, calcium release and the development of stress fibers. Ang-2 inhibits the barrier stabilising effect of Ang-1 thus making the barrier vulnerable to permeability enhancing agents. LPS and TNF-α signalling result in NF-κB nuclear translocation where increased ICAM-1 expression leads to RhoA activation and NO-mediated nitrosylation of junctional proteins. Bradykinin promotes eNOS signalling.