Angiogenesis induced by electrical stimulation is mediated by angiotensin II and VEGF

Objective: Physiological angiogenesis in skeletal muscle is an adaptive res ponse to physical training and electrical stimulation. This study investiga ted the role of angiotensin II (Ang II) in regulating both angiogenesis and vascular endothelial growth factor (VEGF) protein Expression induced by el ectrical stimulation. Methods: The right tibialis anterior (Th) and extensor digitorum longus (ED L) muscles of Sprague-Dawley rats were stimulated for 8 hours per day for 7 days. The contralateral muscles served as controls. Two days before the su rgery and throughout the stimulation protocol. the rats received either lis inopril or losartan in their drinking water. Rats without any drug treatmen t were used as control. Immunohistochemistry and Western blot analysis were performed to identify the sour ce anti quantify! the VEGF protein expressi on in these muscles. The relationship between angiogenesis and VEGF express ion was explored using a VEGF-neutralizing antibody. Results: Chronic electrical stimulation of the skeletal muscles led to sign ificant increases in vessel density (14% and 30% for EDL and TA, respective ly) within 7 days. In addition: stimulation increased VEGF protein levels i n the stimulated muscles. Both lisinopril and losartan blocked elevation in VEGF expression and inhibited the angiogenesis induced by stimulation. VEG F neutralization also inhibited angiogenesis, confirming the relationship b etween Ang II: VEGF, and vessel growth. Conclusion: The current study suggests a pathway involving angiotensin II r eceptors (AT(1)) and VEGF in electrically stimulated angiogenesis.