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By Wafik S. El-Deiry

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Iversen, L. , Mata, J. , and Bylund, D. B. (1999) Bolus intravenous injection of phosphorothioate oligonucleotides causes hypotension by acting as a1-adrenergic receptor antagonists. Toxicol. Appl. Pharmacol. 160, 289–296. , et al. (2001) Local delivery of c-myc neutrally charged antisense oligonucleotides with transport catheter inhibits myointimal hyperplasia and positively affects vascular remodeling in the rabbit balloon injury model. Cathet. Cardiovasc. Interventions 54, 247–256 50 Iversen et al.

ACE-AS-ODNs have also been shown to improve cardiac performance after ischemia-reperfusion injury (81). ACE is present at low to moderate levels in large areas of the brain, and in high levels in the nucleas tractus solitarii (NTS), and is likely to generate Ang II locally (82). Increasing the levels of ACE in the brain by transfection with a plasmid containing the human ACE gene caused an increase in BP, heart rate, and Ang II and ACE levels that lasted 2 wk (83). Unpublished results from our laboratory testing three different sequences of ACE-AS-ODNs showed a decrease in BP in hypertensive SHRs of 15–25 mmHg.

107 Reich, S. , et al. (2003) Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model. Mol. Vis. 9, 210–216. 108. 108 Verma UN, Surabhi, R. , and Gaynor, R. B. (2003) Small interfering RNAs directed against beta-catenin inhibits the in vitro and in vivo growth of colon cancer cells. Clin. Cancer Res. 9, 1291–300. 109. , Mizunno, T. , Mastaitis, J. , and Mobbs, C. V. (2002) Reducing hypothalamic AGRP by RNA interference increases metabolic rate and decreases body weight without influencing food intake.

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