Referenced in: none

Automatically associated channels: Slo1

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

Authors: Marija Marinko, Aleksandra Novakovic, Dragoslav Nenezic, Ivan Stojanovic, Predrag Milojevic, Miomir Jovic, Nenad Ugresić, Vladimir Kanjuh, Qin Yang, Guo-Wei He

Journal, date & volume: J. Pharmacol. Sci., 2015 Jun , 128, 59-64

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25850381

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(+) (KV) channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca(2+)-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 KV channels in HSV is probably due to GC activation and increased levels of cGMP.