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.
Subject(s)
Angiotensin II/physiology , Endothelial Growth Factors/physiology , Lymphokines/physiology , Neovascularization, Physiologic , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Electric Stimulation , Lisinopril/pharmacology , Losartan/pharmacology , Male , Muscle, Skeletal/blood supply , Neovascularization, Physiologic/drug effects , Rats , Rats, Sprague-Dawley , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2 , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
A review was conducted in Haiti to determine the timing and outcome of active tuberculosis (TB) in human immunodeficiency virus (HIV)-positive patients who had previously received isoniazid (INH) prophylaxis. Of 1005 HIV-seropositive patients who completed INH prophylaxis, 14 (1.4%) subsequently had active TB diagnosed. The median interval between discontinuation of INH prophylaxis and TB diagnosis was 8 months for 6 patients receiving 6 months of INH, 22 months for 5 patients receiving 12-24 months of INH, and 40 months for 3 patients receiving 24-36 months of INH (P = .026). There is a postprophylaxis effect on INH that is dependent upon the duration of therapy.
