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Mechanism of vasodilatation with N‐acetylcysteine and NaHS: Contribution of ATP‐sensitive potassium channels
Author(s) -
Yamamoto Michiko,
Adachi Takeshi,
Ishiwata Kyoko,
Ikeda Satsuki,
Hirayama Yoshiaki,
Soga Tomoyoshi,
Suematsu Makoto
Publication year - 2008
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.22.1_supplement.749.14
Subject(s) - chemistry , vasodilation , potassium channel , nitric oxide , vascular smooth muscle , intracellular , hyperpolarization (physics) , cysteine , acetylcysteine , glibenclamide , pharmacology , biochemistry , medicine , stereochemistry , endocrinology , smooth muscle , antioxidant , organic chemistry , nuclear magnetic resonance spectroscopy , enzyme , diabetes mellitus
Objective: Hydrogen sulfide (H 2 S) is known as a toxic gas, however, recent studies reveal H 2 S as the third gaseous vasodilator, following nitric oxide and carbon monoxide. N‐acetylcysteine (NAC) is often used as an anti‐oxidant and it can increase intracellular cysteine (Cys) levels to produce H 2 S. In this study we tested the contribution of ATP‐sensitive potassium channels (IKATP) to NAC‐ and NaHS‐induced relaxation and the metabolic changes induced by H 2 S. Methods: Vascular function was assessed with isometric tension measurement of aortic rings equipped in the organ bath. After aortic constriction with phenyrephrin, a dose‐dependent relaxations to NAC/NaHS (0.3–10 mM) were measured. Some rings were pre‐treated with L‐NAME (100 μM), ODQ (10 μM), or glybenclamide (GLB: 10 μM), an IKATP blocker. Aortic homogenates were prepared and vascular metabolome analysis was performed with capillary electrophoresis/mass spectrometry. Results: Neither L‐NAME nor ODQ affected the aortic relaxations to NAC/NaHS. GLB decreased the maximum relaxation to NaHS. Notably, GLB decreased the speed of relaxation to NAC/NaHS in the early phase. NaHS increased the vascular AMP levels about five folds (31.4±5.8 vs 158.5±31.6 nM). Conclusion: Aortic relaxations to NAC/NaHS are involved with hyperpolarization via the activation of IKATP. An increase in intracellular AMP levels by H 2 S, activates IKATP to modulate vascular tone.