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Activation on nNOS/H 2 O 2 pathway by atorvastatin: implications in the relaxation and endothelial dysfunction induced by lysophosphatidylcholine (851.16)
Author(s) -
Campos Mota Gianne,
NaviaPelaez Juliana,
Lemos Virgínia,
Aggum Capettini Luciano
Publication year - 2014
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.28.1_supplement.851.16
Subject(s) - lysophosphatidylcholine , atorvastatin , nitric oxide , endothelial dysfunction , chemistry , enos , superoxide , vasodilation , medicine , nitric oxide synthase , endocrinology , pharmacology , biochemistry , enzyme , phospholipid , membrane , phosphatidylcholine
Studies of vascular reactivity were performed using aorta thoracic rings of C57BL/6J male mice pre‐incubated with Lysophosphatidylcholine (LPC, 10 µM, 30 minutes). LPC induced endothelial dysfunction characterized by a reduction in acetylcholine response. However pre‐treatment with atorvastatin (Ator, 1 µM, 2h) restored the relaxation. In the presence of Nω‐nitro‐L‐arginine methyl ester (L‐NAME, 300 µM; non‐selective inhibitor of Nitric Oxide Synthase‐NOS) the effect on relaxation was totally bolished. Selective inhibition of nNOS with 1‐[2 ‐ (trifluoromethyl) phenyl] imidazole (TRIM, 300 µM) blocked the improvement of endothelial function induced by Ator. Catalase (2400U/ml, which degrades H2O2, a product of nNOS), also abolished the protective effect of Ator. These results suggest that endotelial dysfunction induced by LPC was reverted by the increase of nNOS activity mediated by Ator. NO and superoxide anion (O 2 ‐ ) production were measured in human endothelial cells by Flow Cytometry using the robes DAF‐FM and DHE, respectively. LPC induced an increase on O 2 ‐ and a decrease in NO production. Ator induced an increase in NO and abolished the O 2 ‐ production by LPC. The effects of Ator in the production of NO and O 2 ‐ was abolished by TRIM. The results suggest that Ator presented a vascular protection mediated by nNOS activation and production of NO and H2O2, improving endotelial function. Grant Funding Source : FAPEMIG, CAPES, CNPq.