Chronic electrical stimulation increased vessel density by 14% and 30% in EDL and TA muscles, an effect blocked by lisinopril, losartan, and VEGF neutralization.
Does angiotensin II blockade prevent angiogenesis and VEGF expression induced by electrical stimulation in skeletal muscle of rats?
Electrical stimulation-induced angiogenesis in skeletal muscle is mediated by an angiotensin II and VEGF-dependent pathway.
OBJECTIVE: Physiological angiogenesis in skeletal muscle is an adaptive response to physical training and electrical stimulation. This study investigated the role of angiotensin II (Ang II) in regulating both angiogenesis and vascular endothelial growth factor (VEGF) protein expression induced by electrical stimulation. METHODS: The right tibialis anterior (TA) and extensor digitorum longus (EDL) 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 surgery and throughout the stimulation protocol, the rats received either lisinopril or losartan in their drinking water. Rats without any drug treatment were used as control. Immunohistochemistry and Western blot analysis were performed to identify the source and quantify the VEGF protein expression in these muscles. The relationship between angiogenesis and VEGF expression was explored using a VEGF-neutralizing antibody. RESULTS: Chronic electrical stimulation of the skeletal muscles led to significant increases in vessel density (14% and 30% for EDL and TA, respectively) within 7 days. In addition, stimulation increased VEGF protein levels in the stimulated muscles. Both lisinopril and losartan blocked elevation in VEGF expression and inhibited the angiogenesis induced by stimulation. VEGF neutralization also inhibited angiogenesis, confirming the relationship between Ang II, VEGF, and vessel growth. CONCLUSION: The current study suggests a pathway involving angiotensin II receptors (AT1) and VEGF in electrically stimulated angiogenesis.
Amaral et al. (Thu,) conducted a other in Physiological angiogenesis in skeletal muscle. Electrical stimulation with lisinopril, losartan, or VEGF-neutralizing antibody vs. Contralateral muscles and rats without drug treatment was evaluated on Vessel density and VEGF protein expression. Chronic electrical stimulation increased vessel density by 14% and 30% in EDL and TA muscles, an effect blocked by lisinopril, losartan, and VEGF neutralization.