Chronic vasodilator treatment intensifies levels of shear stress in capillary beds, stimulating a specific form of angiogenesis, termed longitudinal splitting (Egginton, 2001). The use of the α1-adrenoreceptor antagonist, prazosin is well-established for investigation of this process in skeletal muscle (Baum, 2004). Various studies have explored changes in protein expression during shear stress-induced angiogenesis. However, little attention has focussed on the physiological response to cessation of vasodilator treatment and subsequent regression. Male mice, of the C57BL/10 strain, received prazosin dissolved in tap water (50mg/L) for a period of 4 weeks. In addition to control animals, time points were considered during prazosin treatment (14, 28 days) and the regression phase (3, 7, 14, 28, 42 days; n=4). At sampling, the tibialis anterior muscles were removed, following stunning and cervical dislocation. Assessment of capillary-to-fibre was used to confirm the microvascular response. Angiogenesis was demonstrated by a 15% increase in capillarity after 4 weeks of vasodilator treatment. Upon cessation of treatment, an equivalent decrease represented vessel regression. Changes in protein expression were explored using immunoblotting, with membranes being protein-stained to ensure equal loading of samples. ANOVA was used to assess statistical significance. Interestingly, VEGF levels were seen to decline in response to increases in shear stress, with statistical significance seen (P<0.01), supporting the theory of hyperperfusion (Baum, 2004). Despite this decrease, angiogenesis occurred, reinforcing the suggested role of nitric oxide as an angiogenic factor (Williams, 2006). As expected, increases in eNOS levels were seen in response to prazosin treatment. A mirroring decline from peak eNOS levels was seen during the regression phase, reaching significance after 6 weeks (P<0.05). The expression of the main angiogenic VEGF receptor, Flk-1, increased with shear stress, perhaps compensating for reduced levels of its ligand. Interestingly, Ang-2 levels increased bimodally reflecting its pleiotropic effects, with a 23% increase seen after 2 weeks of prazosin treatment. Following a brief decrease, a further 74% increase occurred during vessel regression. The effects of this cytokine were clearly dependent on associated levels of VEGF. We conclude that this form of angiogenesis involves both a rapid phase on induction and regression following withdrawal of stimulus. All procedures follow current UK legislation