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Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts

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2015
2459.pdf (671.6Kb)
Authors
Marinko, Marija
Novaković, Aleksandra
Nenezić, Dragoslav
Stojanović, Ivan
Milojević, Predrag
Jović, Miomir
Ugrešić, Nenad
Kanjuh, Vladimir
Yang, Qin
He, Guo-Wei
Article (Published version)
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Abstract
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 vasorelax...ant 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.

Keywords:
Nicorandil / Cyclic GMP / K channel / Vasorelaxation / Human bypass grafts
Source:
Journal of Pharmacological Sciences, 2015, 128, 2, 59-64
Publisher:
  • Japanese Pharmacological Soc, Kyoto
Projects:
  • Investigation of the Effect and Mechanism of Action of Different Vasodilator Substances on the Human Bypass Grafts (RS-175088)

DOI: 10.1016/j.jphs.2015.03.003

ISSN: 1347-8613

PubMed: 25850381

WoS: 000357472000001

Scopus: 2-s2.0-84937396257
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URI
http://farfar.pharmacy.bg.ac.rs/handle/123456789/2461
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Pharmacy

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