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Publication : Lack of critical involvement of endothelial nitric oxide synthase in vascular nitrate tolerance in mice.

First Author  Wang EQ Year  2002
Journal  Br J Pharmacol Volume  135
Issue  2 Pages  299-302
PubMed ID  11815364 Mgi Jnum  J:103179
Mgi Id  MGI:3608590 Doi  10.1038/sj.bjp.0704532
Citation  Wang EQ, et al. (2002) Lack of critical involvement of endothelial nitric oxide synthase in vascular nitrate tolerance in mice. Br J Pharmacol 135(2):299-302
abstractText  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 x 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 approximately 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.
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