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(Hypertension. 2001;38:210.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Human Heme Oxygenase-1 Gene Transfer Lowers Blood Pressure and Promotes Growth in Spontaneously Hypertensive Rats
From the Departments of Pharmacology (H.E.S., F.Z., A.N., M.S., A.K., N.G.A.) and Pathology (A.E.), New York Medical College, Valhalla; Rockefeller University (M.S., A.K., N.G.A.), New York, NY; and Department of Pediatrics, Stanford University School of Medicine (X.N., P.D.), Calif.
Correspondence to Professor Nader G. Abraham, Department of Pharmacology, New York Medical College, Valhalla, NY 10595. E-mail nader_abrham{at}nymc.edu
Abstract—— Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5x109 to 1x1010 colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats.
Key Words: hypertension • heme oxygenase-1 • retrovirus • gene transfer • growth
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