The Relaxant Action of Nicorandil in Bovine Tracheal Smooth Muscle

Abstract

The relaxant mechanisms of nicorandil were examined by comparing its effects with those of sodium nitroprusside and cromakalim in bovine tracheal smooth muscle. In preparations contracted with methacholine (0.3 µmol/l) or high K⁺ (40 mmol/l), nicorandil and sodium nitroprusside caused concentration-dependent relaxations. Their relaxant effects on high K⁺-contracted preparations were smaller than those on methacholine-contracted muscle. Cromakalim relaxed methacholine-contracted preparations, whereas it had no effect on high K⁺-contracted muscle. The inhibitor of soluble guanylyl cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 5 µmol/l) completely prevented the relaxation induced by lower concentrations (<30 µmol/l) of nicorandil, whereas it partially attenuated relaxation caused by higher concentrations. The ATP-sensitive K⁺ (K_ATP) channel blocker glibenclamide only partially attenuated the relaxant responses to nicorandil (at 100 and 300 µmol/l). Combination treatment with ODQ and glibenclamide almost completely prevented nicorandil-induced relaxations. The large-conductance Ca²⁺-activated K⁺ channel (Maxi K⁺ channel) inhibitor iberiotoxin significantly prevented the relaxations induced by lower concentrations (3 and 10 µmol/l) of nicorandil. The preventive effect of iberiotoxin was markedly enhanced under the blockade of K_ATP channels with glibenclamide. These results suggest that nicorandil relaxes bovine tracheal smooth muscle through 2 mechanisms: opening of K_ATP channels and activation of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Nicorandil may also activate Maxi K⁺ channels, possibly through the NO-cGMP pathway, and the interaction of K_ATP channels and Maxi K⁺ channels may affect the relaxant effect of nicorandil in bovine tracheal smooth muscle.

Insight into the Mechanisms Underlying the Tracheorelaxant Properties of the Sideritis raeseri Extract

“…Isometric tension was continuously measured with a force transducer (DMT 750, Danish Myo Technology, Denmark). The trachea segments were manually stretched initially to 1 g initial tension, which was found to be optimal for measuring the changes in tension [ 11 , 16 , 17 ]. This passive tension was applied throughout the experiment, and subsequent changes in tension were recorded continuously using the PowerLab system with LabChart software (ADI Instruments, Denmark).…”