Overexpression of eNOS prevents the development of renovascular hypertension in mice

Abstract

Gene therapy has become an important tool for understanding several cardiovascular diseases. In the present study we investigated the effects of endothelial nitric oxide synthase (eNOS) overexpression on renovascular hypertension. Experiments were carried out in C57BL/6 mice randomly assigned to either a two-kidney one-clip (2K1C) hypertension group or a sham-operated group. At the same time surgery was carried out, both 2K1C and sham mice received an intravenous injection of recombinant adenovirus expressing the functional gene eNOS or the reporter gene β-galactosidase (β-gal). Fourteen days later, arterial pressure, baroreflex sensitivity, and cardiac sympathetic and parasympathetic tone were evaluated in conscious mice. Measurement of mean arterial pressure showed arterial hypertension in 2K1C-βgal mice compared with sham-βgal mice (121 ± 3 vs. 96 ± 2 mm Hg, p < 0.01), which was prevented by eNOS overexpression (2K1C-eNOS 100 ± 4 vs. sham-eNOS 99 ± 3 mm Hg). Linear regression analysis of the reflex tachycardia response to sodium nitroprusside-induced hypotension showed that baroreflex sensitivity was significantly attenuated in 2K1C-βgal mice (5.8 ± 0.5 vs. sham-βgal 8.0 ± 0.8 beats·min–1·mm Hg–1, p < 0.05), but this decrease was not prevented by eNOS overexpression (2K1C-eNOS 7.2 ± 0.5 vs. sham-eNOS 8.8 ± 0.7 beats·min–1·mm Hg–1, p < 0.05). The cardiac sympathetic tone was augmented and the vagal tone was reduced in 2K1C-βgal (152 ± 17 and 45 ± 12 beats·min–1, respectively) compared with sham-βgal mice (112 ± 6 and 89 ± 7 beats·min–1, respectively), and similar results were observed in 2K1C-eNOS mice compared with sham-eNOS. The data indicate that eNOS overexpression was able to prevent the development of 2K1C renovascular hypertension in mice, without affecting other characteristic cardiovascular dysfunctions.