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Nitrite enhances ischemia‐induced angiogenesis by Nitric Oxide dependent pathway
Author(s) -
Kumar Dinesh,
Branch Billy,
Arora Neeraj,
Kaushal Kirti,
Senthilkumar Annamalai,
Glawe John,
Chidlow John,
Teng Xinjun,
Brown Melissa,
Lefer David,
Patel Rakesh,
Kevil Christopher
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a13-d
Subject(s) - nitrite , nitric oxide , nitrate , ischemia , medicine , blood flow , anesthesia , pharmacology , chemistry , organic chemistry
Purpose: We tested the hypothesis that in permanent ischemia, nitrite would enhance angiogenesis as compared to nitrate or PBS Methods: Hind limb ischemia was induced by femoral artery ligation. Nitrite and nitrate were given intraperitoneally in 2 doses 3.3mg/kg and 165μg/kg twice a day for 7 days. PBS injections served as control. Blood flow was measured with Laser Doppler on days 0, 3, 5 and 7. Angiogenic index (AI), cGMP, tissue and blood nitrite (TBN) were done on days 3 and 7. Next, NO scavenger PTIO was used with nitrite 165μg/kg Results: Blood Flow and AI were significantly increased in nitrite treated ischemic limbs vs. control (AI 165: 1.2 vs. 0.4; AI 3.3: 0.6 vs. 0.3 p<0.0001) Both doses of nitrite were better than nitrate. AI was better with the lower dose of 165μg/kg of nitrite as compared to 3.3mg/kg. At day 3, TBN increased in nitrite treated ischemic limbs but this resolved by day 7. Tissue cGMP was elevated in nitrite treated limbs compared to nitrate ischemic limbs at 3.3mg/kg dose but was lower than nitrate at 165μg/kg dose. Blood flow response with 165μg/kg nitrite was completely abolished in presence of PTIO demonstrating NO dependence. Conclusion: Nitrite enhances angiogenesis in response to permanent ischemia via nitric oxide pathway and is a novel therapy in peripheral artery disease and transplant medicine.