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Lack of critical involvement of endothelial nitric oxide synthase in vascular nitrate tolerance in mice
Author(s) -
Wang Ellen Q,
Lee WooIn,
Fung HoLeung
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704532
Subject(s) - enos , nitric oxide , nitric oxide synthase type iii , nitric oxide synthase , medicine , knockout mouse , endocrinology , chemistry , endothelial nitric oxide synthase , western blot , nitrate , pharmacology , biochemistry , receptor , organic chemistry , gene
We examined the direct involvement of endothelial nitric oxide (eNOS) in nitrate tolerance using eNOS knockout (eNOS (−/−)) and wild‐type (eNOS (+/+)) mice. Animals were treated with either nitroglycerin (NTG, 20 mg kg −1 s.c. 3×daily for 3 days) or vehicle (5% dextrose, D5W), and nitrate tolerance was assessed ex vivo in isolated aorta by vascular relaxation studies and cyclic GMP accumulation. Western blot was performed to determine NOS expression after NTG treatment. In both the eNOS (−/−) and (+/+) mice, the EC 50 from NTG concentration‐response curve was increased by ∼3 fold, and vascular cyclic GMP accumulation was similarly decreased after NTG pretreatment. Vascular tolerance did not lead to changes in eNOS protein expression in eNOS (+/+) mice. These results indicate that vascular nitrate tolerance was similarly induced in eNOS (−/−) and (+/+) mice, suggesting that eNOS may not be critically involved in nitrate tolerance development in mice. British Journal of Pharmacology (2002) 135 , 299–302; doi: 10.1038/sj.bjp.0704532