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

2015
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)
Metadata
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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 graftsSource:
Journal of Pharmacological Sciences, 2015, 128, 2, 59-64Publisher:
- Japanese Pharmacological Soc, Kyoto
Funding / projects:
DOI: 10.1016/j.jphs.2015.03.003
ISSN: 1347-8613
PubMed: 25850381
WoS: 000357472000001
Scopus: 2-s2.0-84937396257
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PharmacyTY - JOUR AU - Marinko, Marija AU - Novaković, Aleksandra AU - Nenezić, Dragoslav AU - Stojanović, Ivan AU - Milojević, Predrag AU - Jović, Miomir AU - Ugrešić, Nenad AU - Kanjuh, Vladimir AU - Yang, Qin AU - He, Guo-Wei PY - 2015 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2461 AB - 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. PB - Japanese Pharmacological Soc, Kyoto T2 - Journal of Pharmacological Sciences T1 - Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts VL - 128 IS - 2 SP - 59 EP - 64 DO - 10.1016/j.jphs.2015.03.003 ER -
@article{ author = "Marinko, Marija and Novaković, Aleksandra and Nenezić, Dragoslav and Stojanović, Ivan and Milojević, Predrag and Jović, Miomir and Ugrešić, Nenad and Kanjuh, Vladimir and Yang, Qin and He, Guo-Wei", year = "2015", 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 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.", publisher = "Japanese Pharmacological Soc, Kyoto", journal = "Journal of Pharmacological Sciences", title = "Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts", volume = "128", number = "2", pages = "59-64", doi = "10.1016/j.jphs.2015.03.003" }
Marinko, M., Novaković, A., Nenezić, D., Stojanović, I., Milojević, P., Jović, M., Ugrešić, N., Kanjuh, V., Yang, Q.,& He, G.. (2015). Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts. in Journal of Pharmacological Sciences Japanese Pharmacological Soc, Kyoto., 128(2), 59-64. https://doi.org/10.1016/j.jphs.2015.03.003
Marinko M, Novaković A, Nenezić D, Stojanović I, Milojević P, Jović M, Ugrešić N, Kanjuh V, Yang Q, He G. Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts. in Journal of Pharmacological Sciences. 2015;128(2):59-64. doi:10.1016/j.jphs.2015.03.003 .
Marinko, Marija, Novaković, Aleksandra, Nenezić, Dragoslav, Stojanović, Ivan, Milojević, Predrag, Jović, Miomir, Ugrešić, Nenad, Kanjuh, Vladimir, Yang, Qin, He, Guo-Wei, "Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts" in Journal of Pharmacological Sciences, 128, no. 2 (2015):59-64, https://doi.org/10.1016/j.jphs.2015.03.003 . .