《Bradycardia In Vivo》.pdfVIP

Overexpression of eNOS in NTS Causes Hypotension and Bradycardia In Vivo Koji Sakai, Yoshitaka Hirooka, Isamu Matsuo, Kenichi Eshima, Hideaki Shigematsu, Hiroaki Shimokawa, Akira Takeshita Abstract—The role of nitric oxide (NO) in the brain in the control of blood pressure and the sympathetic nervous system is debated. This study examined the effect of overexpression of endothelial NO synthase (eNOS) in the nucleus tractus solitarii (NTS) on blood pressure in conscious rats. Adenovirus vectors encoding either eNOS (AdeNOS) or -galactosidase were transfected into the NTS in vivo. In the AdeNOS-treated rats, the local expression of eNOS in the NTS was confirmed by immunohistochemical staining and Western blot analysis for the eNOS protein and by increased production of nitrite/nitrate in the NTS measured by in vivo microdialysis. Blood pressure and heart rate, monitored by the use of a radiotelemetry system in a conscious state, were significantly decreased in the AdeNOS-treated group at day 5 to day 10 after the gene transfer. Urinary norepinephrine excretion also was decreased at day 7 after the gene transfer in the AdeNOS-treated group. Our results indicate that overexpression of eNOS in the NTS decreases blood pressure, heart rate, and sympathetic nerve activity in conscious rats. (Hypertension. 2000;36:1023-1028.) Key Words: genes nitric oxide brain sympathetic nervous system There is considerable evidence that nitric oxide (NO) in regions on the regulation of blood pressure and sympathetic the brain affects sympathetic nerve activity and modu- nerve activity in conscious animals remain to be clarified. lates blood pressure and heart rate.1–6 Studies that used