The effect of the K+ agonist nicorandil on peripheral vascular resistance

Background The vasoactive effect of nicorandil on coronary arteries is well known. Nicorandil exerts its vasodilatory effect through a dual mechanism of action: involving on the one hand cyclic guanosine monophosphate (c GMP) as a nitrovasodilatator, and on the other hand, acting as a potassium channel opener. Objective To address the question if nicorandil works in peripheral arteries, its effect on peripheral vascular resistance was evaluated in isolated perfused guinea pig hind limbs. Methods A catheter was inserted via the distal aorta and common iliac artery. Perfusion pressure was monitored under constant perfusion with Tyrodeʹs solution, therefore changes in perfusion pressure represent changes in vascular resistance. After stabilization precontraction of the peripheral vascular bed was achieved with noradrenaline 3 μM and nicorandil was added in concentrations of 1, 10 and 100 μM. The effect of nicorandil (1, 10 and 100 μM) was tested in the presence of l-NAME and glybenclamide. Results A significant reduction of vascular peripheral resistance was already achieved at a concentration of 1 μM nicorandil (30.3 ± 6.1%, mean S.E.M., p < 0.001). At a concentration of 100 μM nicorandil the reduction of peripheral vascular resistance was 94.4 ± 16.4%. Peripheral vascular resistance was less but nearly comparable reduced by nicorandil (100 μM) if the endothelial NO effect was inhibited by l-NAME (58.6 ± 18.6%) or if the ATP-dependent potassium channels were blocked by glybenclamide (56.4 ± 14.6%). Conclusions In peripheral arteries the nitrovasodilator effect of nicorandil is nearly comparable to the potassium agonistic effect, and the concentration, which is necessary to reduce peripheral vascular resistance significantly, is comparable with dosages necessary for reduction of coronary resistance.