Abstract 523: Sodium Nitrite Therapy Augments Ischemia-Induced Neovascularization and Blood Flow Recovery in Different Models of Hypertension

Autor: Ali Amin, Sookyoung Choi, Y Osman-Elazeik, N Badr El-Din, C G Kevil, G L Navar, P Kadowitz, M Trebak, Khalid Matrougui
Rok vydání: 2012
Předmět:
Zdroj: Hypertension. 60
ISSN: 1524-4563
0194-911X
DOI: 10.1161/hyp.60.suppl_1.a523
Popis: Background: Arterial hypertension is a major risk factor that can lead to exacerbation of peripheral vascular disease due, in part, to endothelial dysfunction. Because sodium nitrite (SN) can be converted to nitric oxide (NO), which counteracts endothelial dysfunction, we explored the effect of nitrite on neovascularization following hind-limb ischemia in different models of hypertension (HT). METHODS: Chronic infusion of angiotensin-II (Ang-II, 400ng/Kg/min) or N(omega)-nitro-L-arginine-methyl-ester (L-NAME, 0.1g/L) were used for a two week period to induce hypertension. Mice were subjected to femoral artery ligation induced-ischemia in the hind-limb followed by treatment with SN (50mg/L) for 2-weeks. Results: SN significantly reduced systolic arterial blood pressure in mice receiving Ang-II and L-NAME, but had no effect in sham animals. After 2 weeks, blood flow and microangiography showed 60% recovery in sham compared to 40% in HT mice. Importantly, sham and HT mice treated with SN had a 100% blood flow recovery associated with normalization in capillary density. The inhibition of xanthine-oxido-reductase (allopurinol) or VEGFR (SU-5416) prevented the neovascularization in HT mice treated with SN. Cyclic GMP (cGMP) content in the hind-limb was significantly increased in mice treated with SN compared to non-treated mice. Nitrite/nitrate content was only increased in the sham group treated with SN. Immunoprecipitation and Western blot analysis revealed an increase in eNOS/Akt/VEGFR phosphorylation in skeletal muscle from mice treated with SN compared to non-treated mice. Conclusion: Our findings determine that SN therapy rescues the neovascularization and blood flow recovery in ischemic hind-limb of sham and HT mice likely through the Akt/NO/cGMP and VEGFR pathways.
Databáze: OpenAIRE
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