Faculty Collaboration Database

Angiogenesis induced by electrical stimulation is mediated by angiotensin II and VEGF. Microcirculation 2001 Feb;8(1):57-67

Date

04/12/2001

Pubmed ID

11296854

Scopus ID

2-s2.0-0035260068 (requires institutional sign-in at Scopus site)   117 Citations

Abstract

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.

Author List

Amaral SL, Linderman JR, Morse MM, Greene AS

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Animals
Electric Stimulation
Endothelial Growth Factors
Lisinopril
Losartan
Lymphokines
Male
Muscle, Skeletal
Neovascularization, Physiologic
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors