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TOLERANCE TO NITROGLYCERIN IS DUE TO eNOS UNCOUPLING.
Author(s) -
Rezende Dias Vania Braghini,
Silva Bruno Rodrigues,
Grando Marcella Daruge,
Bendhack Lusiane Maria
Publication year - 2013
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.27.1_supplement.1196.3
Subject(s) - enos , phosphorylation , chemistry , vasodilation , nitric oxide , incubation , medicine , endocrinology , endothelium , pharmacology , biochemistry , nitric oxide synthase
The mechanisms underlying the tolerance induced by nitroglycerin (NTG) and the contribution of endothelial cells (EC) remain unclear. In this regard, NTG could activate eNOS acting as a signal amplifier pathway eNOS phosphorylation in the residue Ser 1177 . We have verified that the endothelium modulates the vasodilatation induced by NTG in rat aorta and the in vitro tolerance was induced after 5 minutes incubation with NTG (EC 100 ). This study aimed to investigate the effects of (i) addition of NOS cofactor BH 4 , (ii) the expression of eNOS and (iii) phosphorylation of Ser 1177 on eNOS NTG‐induced relaxation during tolerance. Incubation with the NOS cofactor BH 4 reversed the potency of NTG‐induced tolerance (pD 2 from 7.63 ± 0.08 to 8.27: ± 0.07) and efficacy (from 54.7±3.6% to 94.5±2.5% P<0.001). No changes were observed in the phosphorylation of Ser 1177 , the activation site of eNOS when compared with control (0.225±0.030 vs 0.159±0.0270, n = 7/group). Therefore, our results suggest that NTG‐induced aorta tolerance in a short‐time may involve eNOS uncoupling, but not phosphorylation of Ser 1177 . Supported by FAPESP and CNPq.