Gene Transfer of Extracellular Superoxide Dismutase Reduces Arterial Pressure in Spontaneously Hypertensive Rats: Role of Heparin-Binding Domain

• Published in: Circulation research 2003-03, Vol.92 (4), p.461-468
• Main Authors: Chu, Yi, Iida, Shinichiro, Lund, Donald D, Weiss, Robert M, DiBona, Gerald F, Watanabe, Yoshimasa, Faraci, Frank M, Heistad, Donald D
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Anesthesia; Animals; Arterial hypertension. Arterial hypotension; Binding Sites - genetics; Biological and medical sciences; Biotechnology; Blood and lymphatic vessels; Blood Pressure - physiology; Cardiac Output - physiology; Cardiology. Vascular system; Consciousness; Experimental diseases; Fundamental and applied biological sciences. Psychology; Gene therapy; Genetic Therapy - methods; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Health. Pharmaceutical industry; Heparin - metabolism; Humans; Hypertension - genetics; Hypertension - physiopathology; Hypertension - therapy; Industrial applications and implications. Economical aspects; Injections, Intravenous; Male; Medical sciences; Mutation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Time Factors
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.0000057755.02845.F9

ABSTRACT—Oxidative stress may contribute to hypertension. The goals of this study were to determine whether extracellular superoxide dismutase (ECSOD) reduces arterial pressure in spontaneously hypertensive rats (SHR) and whether its heparin-binding domain (HBD), which is responsible for cellular binding, is necessary for the function of ECSOD. Three days after intravenous injection of an adenoviral vector expressing human ECSOD (AdECSOD), mean arterial pressure (MAP) decreased from 165±4 mm Hg (mean±SE, n=7) to 124±3 mm Hg (n=7) in adult anesthetized SHR (P