P151Different potassium channels are involved in relaxation of arterial graft induced by nicorandil

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Abstract

The drug nicorandil is a vasodilator approved for treatment of angina. In addition to its well-known effect on the opening of ATP-sensitive K+ (KATP) channels, nicorandil-induced vasorelaxation also involves the opening of Ca2+-activated K+ (KCa) channels.

Purpose

The aim of this study was to investigate the effects of nicorandil, K+ channel opener, on the isolated human internal mammary artery (HIMA) and to define the contribution of different K+ channel subtypes in nicorandil action on this blood vessel.

Methods

The HIMA segments were collected from male patients suffering from coronary artery disease who were undergoing coronary artery bypass surgery and studied in organ bath. HIMA rings were pre-contracted with phenylephrine (10 μM). Endothelium was removed mechanically.

Results

Our results show that nicorandil (0.001 μM – 300 μM) induced a concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Glibenclamide (10 μM), a selective KATP channels inhibitor, as well as iberiotoxin (100 nM), a most selective blocker of large-conductance KCa (BKCa) channels, partly antagonized relaxation of HIMA induced by nicorandil. In contrast, a non-selective blocker of voltage-gated K+ (KV) channels, 4-aminopyridine (4 AP, 0.5 mM), as well as margatoxin (10 nM), a potent inhibitor of KV1.3 channels, did not abolish the nicorandil-induced relaxation of HIMA.

Conclusions

Our results showed that nicorandil induced strong endothelium-independent relaxation of HIMA. It seems that KATP and BKCa channels located in the smooth muscle of HIMA mediated relaxation induced by nicorandil.

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