期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 128, 期 2, 页码 59-64出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2015.03.003
关键词
Nicorandil; Cyclic GMP; K channel; Vasorelaxation; Human bypass grafts
资金
- Scientific Research Grant from Ministry of Science and Technology Serbia [P175088]
- Serbian - Chinese Science & Technology Cooperation [680-00-00557/2013-09/13]
- National Natural Science Foundation of China [81170148]
- National Basic Research Program of China [2010CB529500]
- Tianjin Binhai New Area Health Bureau [2011BHKZ001]
As we previously demonstrated the role of different K+ channels in the action of nicorandil on human saphenous vein (HSV) and human internal mammary artery (HIMA), this study aimed to analyse the contribution of the cGMP pathway in nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the K+ channel-activating effect of nicorandil. An inhibitor of soluble guanylate cyclase (GC), ODQ, significantly inhibited nicorandil-induced relaxation, while ODQ plus glibenclamide, a selective ATP-sensitive K+ (KATP) channel inhibitor, produced a further inhibition of both vessels. In HSV, ODQ in combination with 4-aminopyridine, a blocker of voltage-gated K+ (K-V) channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca2+-activated K+ (BKCa) channels, produced greater inhibition than ODQ alone. We showed that the cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on HSV and HIMA. It seems that nicorandil directly opens KATP channels in both vessels and BKCa channels in HIMA, although it is possible that stimulation of GC contributes to KATP channels activation in HIMA. Contrary, the activation of K-V channels in HSV is probably due to GC activation and increased levels of cGMP. (C) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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