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Hydrogen peroxide-induced vascular relaxation in porcine coronary arteries is mediated by Ca2+-activated K+ channels

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Summary

Hydrogen peroxide (H2O2) elicited concentration-dependent relaxation of endothelium-denuded rings of porcine coronary arteries. The relaxation induced by the H2O2 was markedly attenuated by 10μM 1H-[1,2,4]oxadiazolo [4,3,a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase, or by 100nM charybdotoxin, an inhibitor of large-conductance Ca2+-activated K+ (KCa) channels. A combination of the ODQ and charybdotoxin abolished the H2O2-induced relaxation. Pretreatment with 25 μM of an Rp stereoisomer of adenosine-3′,5′-cyclic monophosphothioate (Rp-cAMPS), 20μM glibenclamide, or 1mM 4-aminopyridine did not affect the vascular response to H2O2. The presence of catalase at 1000U/ml significantly attenuated the H2O2-induced relaxation. Exposure of cultured smooth muscle cells to H2O2 activated KCa channels in a concentration-dependent manner in cell-attached patches. Pretreatment with catalase significantly inhibited the activation of KCa channels. Rp-cAMPS did not inhibit the H2O2-induced activation of KCa channels. The activation of KCa channels by H2O2 was markedly decreased in the presence of ODQ. However, even in the presence of ODQ, H2O2 activated KCa channels in a concentration-dependent manner. In inside-out patches, H2O2 significantly activated KCa channels through a process independent of cyclic guanosine 3′,5′-monophosphate (cGMP). In conclusion, H2O2 elicits vascular relaxation due to activation of KCa channels, which is mediated partly by a direct action on the channel and partly by activation of soluble guanylate cyclase, resulting in the generation of cGMP.

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Authors and Affiliations

  1. Department of Pediatrics School of Medicine, University of Tokushima, Kuramoto-cho-2, 770-8503, Tokushima, Japan

    Yasunobu Hayabuchi, Suguru Matsuoka & Yasuhiro Kuroda

  2. Department of Nutrition, School of Medicine, University of Tokushima, Kuramoto-cho-2, 770-8503, Tokushima, Japan

    Yutaka Nakaya

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  1. Yasunobu Hayabuchi
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  2. Yutaka Nakaya
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  3. Suguru Matsuoka
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  4. Yasuhiro Kuroda
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Hayabuchi, Y., Nakaya, Y., Matsuoka, S. et al. Hydrogen peroxide-induced vascular relaxation in porcine coronary arteries is mediated by Ca2+-activated K+ channels. Heart Vessels 13, 9–17 (1998). https://doi.org/10.1007/BF02750638

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  • DOI: https://doi.org/10.1007/BF02750638

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