Sodium nitrite therapy rescues ischemia-induced neovascularization and blood flow recovery in hypertension.

Ali Amin, Soo Kyoung Choi, Yehia Osman-Elazeik, Nariman K. Badr El-Din, Christopher G. Kevil, Louis G. Navar, Philip Kadowitz, Mohamed Trebak, Khalid Matrougui

Research output: Contribution to journalArticle

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Abstract

Arterial hypertension is a major risk factor that can lead to complication 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). Chronic delivery of angiotensin II (Ang II, 400 ng/kg/min) or N(omega)-nitro-L-arginine-methyl-ester (L-NAME, 0.1 g/L) was used for a 2-week period to induce hypertension. Mice were subjected to femoral artery ligation-induced ischemia in the hind limb followed by treatment with SN (50 mg/L) for 2 weeks. 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 % ± 1.0 recovery in sham compared with 40 % ± 1.3 in HT mice. Importantly, sham and HT mice treated with SN showed 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 with 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 with non-treated mice. Our findings indicate that SN therapy rescues the neovascularization and blood flow recovery in the ischemic hind limb of sham and HT mice likely through the Akt/NO/cGMP and VEGFR pathways.

Original languageEnglish (US)
Pages (from-to)583-592
Number of pages10
JournalPflügers Archiv : European journal of physiology
Volume464
Issue number6
DOIs
StatePublished - Jan 1 2012

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Sodium Nitrite
Blood
Ischemia
Hypertension
Recovery
NG-Nitroarginine Methyl Ester
Extremities
Therapeutics
Cyclic GMP
Nitrites
Nitric Oxide
Allopurinol
Phosphorylation
Xanthine
Blood pressure
Peripheral Vascular Diseases
Angiotensin II
Femoral Artery
Nitrates
Immunoprecipitation

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

Amin, A., Choi, S. K., Osman-Elazeik, Y., Badr El-Din, N. K., Kevil, C. G., Navar, L. G., ... Matrougui, K. (2012). Sodium nitrite therapy rescues ischemia-induced neovascularization and blood flow recovery in hypertension. Pflügers Archiv : European journal of physiology, 464(6), 583-592. https://doi.org/10.1007/s00424-012-1167-y
Amin, Ali ; Choi, Soo Kyoung ; Osman-Elazeik, Yehia ; Badr El-Din, Nariman K. ; Kevil, Christopher G. ; Navar, Louis G. ; Kadowitz, Philip ; Trebak, Mohamed ; Matrougui, Khalid. / Sodium nitrite therapy rescues ischemia-induced neovascularization and blood flow recovery in hypertension. In: Pflügers Archiv : European journal of physiology. 2012 ; Vol. 464, No. 6. pp. 583-592.
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abstract = "Arterial hypertension is a major risk factor that can lead to complication 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). Chronic delivery of angiotensin II (Ang II, 400 ng/kg/min) or N(omega)-nitro-L-arginine-methyl-ester (L-NAME, 0.1 g/L) was used for a 2-week period to induce hypertension. Mice were subjected to femoral artery ligation-induced ischemia in the hind limb followed by treatment with SN (50 mg/L) for 2 weeks. 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 {\%} ± 1.0 recovery in sham compared with 40 {\%} ± 1.3 in HT mice. Importantly, sham and HT mice treated with SN showed 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 with 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 with non-treated mice. Our findings indicate that SN therapy rescues the neovascularization and blood flow recovery in the ischemic hind limb of sham and HT mice likely through the Akt/NO/cGMP and VEGFR pathways.",
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Amin, A, Choi, SK, Osman-Elazeik, Y, Badr El-Din, NK, Kevil, CG, Navar, LG, Kadowitz, P, Trebak, M & Matrougui, K 2012, 'Sodium nitrite therapy rescues ischemia-induced neovascularization and blood flow recovery in hypertension.', Pflügers Archiv : European journal of physiology, vol. 464, no. 6, pp. 583-592. https://doi.org/10.1007/s00424-012-1167-y

Sodium nitrite therapy rescues ischemia-induced neovascularization and blood flow recovery in hypertension. / Amin, Ali; Choi, Soo Kyoung; Osman-Elazeik, Yehia; Badr El-Din, Nariman K.; Kevil, Christopher G.; Navar, Louis G.; Kadowitz, Philip; Trebak, Mohamed; Matrougui, Khalid.

In: Pflügers Archiv : European journal of physiology, Vol. 464, No. 6, 01.01.2012, p. 583-592.

Research output: Contribution to journalArticle

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T1 - Sodium nitrite therapy rescues ischemia-induced neovascularization and blood flow recovery in hypertension.

AU - Amin, Ali

AU - Choi, Soo Kyoung

AU - Osman-Elazeik, Yehia

AU - Badr El-Din, Nariman K.

AU - Kevil, Christopher G.

AU - Navar, Louis G.

AU - Kadowitz, Philip

AU - Trebak, Mohamed

AU - Matrougui, Khalid

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