title: Angiogenesis induced by electrical stimulation is mediated by angiotensin II and VEGF.
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.
  
  
  CONCLUSIONS
  The current study suggests a pathway involving angiotensin II receptors (AT1) and VEGF in electrically stimulated angiogenesis.
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee 53226-0509, USA.
authors: S L
authors: SL
authors: Amaral
authors: J R
authors: JR
authors: Linderman
authors: M M
authors: MM
authors: Morse
authors: A S
authors: AS
authors: Greene
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D016228:Endothelial Growth Factors / Q000502:physiology*; D017706:Lisinopril / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008222:Lymphokines / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016228:Endothelial Growth Factors; D008222:Lymphokines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000804:Angiotensin II; D017706:Lisinopril; D019808:Losartan