A potential role for Angiotensin II in skeletal muscle overload induced angiogenesis

Muscle overload induces a characteristic pattern of capillary growth through abluminal sprouting, which is dependent on both vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Angiotensin (Ang) II is involved in the response to altered muscle activity and has a documented role in VEGF production. In this study we investigated the effect of Ang II stimulation on endothelial cell VEGF and MMP‐2 production and ascertained the importance of Ang II signalling to the angiogenic response to rat skeletal muscle overload. While Ang II stimulation of skeletal muscle microvascular endothelial cells had no effect on VEGF or MMP‐2 mRNA production, VEGF protein levels were significantly elevated with overnight Ang II treatment (1.41 ± 0.09 vs. 1.00 ± 0.06 for control). Extensor digitorum longus muscle overload was induced through unilateral extirpation of the synergist muscle tibialis anterior and the role of Ang II was assessed through delivery of the AT1 receptor inhibitor losartan (20mg/kg/day). Losartan did not attenuate the overload‐induced increase in capillary to muscle fibre ratio (overload alone − 2.34 ± 0.06 vs. 2.54 ± 0.14 for overload + losartan), indicating that Ang II signalling via the AT1 receptor does not play a critical role in the angiogenic response to skeletal muscle overload. Funding by NSERC.