Pharmacological characterization of nicorandil by 86Rb efflux and isometric vasorelaxation studies in vascular smooth muscle.
Nicorandil and cromakalim were found to stimulate 86Rb efflux (a marker of K+ ions) from resting preparations of rabbit aorta. This action was suppressed by 10(-5) M glibenclamide, an antagonist of K(+)-channel openers in vascular smooth muscle. Through intracellular production of cyclic GMP, and subsequent suppression of cellular Ca2+ activation, nitrovasodilators interfere indirectly with the activation of Ca(2+)-dependent ion channels. 8-Bromo-cyclic GMP and sodium nitroprusside antagonized the Ca(2+)-dependent 86Rb efflux induced by 3 x 10(-7) M norepinephrine. When nicorandil and cromakalim were investigated in the same experimental setup in the presence of glibenclamide to suppress stimulation of K+ channels, only nicorandil also suppressed the norepinephrine-induced increase of the 86Rb efflux. These results confirm that nicorandil acts as both an opener of K+ channels and a nitrovasodilator. Nicorandil relaxed helical strips from rabbit aorta contracted by 10(-7) M norepinephrine, but in contrast to the relaxant action of cromakalim, this response was not antagonized by the use of glibenclamide, indicating a greater importance of the nitrovasodilator mechanism than of the K(+)-channel-opening activity for relaxation in this tissue. However, when the nitrate-like action of nicorandil was suppressed by 10(-5) M methylene blue, the K(+)-channel-opening activity was unmasked on addition of 10(-4) M glibenclamide at high concentrations of nicorandil.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D009599:Nitroprusside / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D012414:Rubidium Radioisotopes; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; D009536:Niacinamide; D020108:Nicorandil; D005905:Glyburide