Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats

Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with re lease of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector con taining human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purifi cation and concentration of the viral particles to achieve 5 X 10(9) to 1 X 10(10) colony-forming units per milliliter. The ability of concentrated in fectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral partic les (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulte d in functional expression of the HHO-1 gene and attenuation of the develop ment of hypertension. Rats expressing HHO-1 showed a significant decrease i n urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isola ted arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous sig nificant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and pr omotes body growth in spontaneously hypertensive rats.