Pharmacological Characterization of Nicorandil by 86Rb Efflux and Isometric Vasorelaxation Studies in Vascular Smooth Muscle

Publisher Website
Google Scholar
Abstract
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 10−5M 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 Ca2+-dependent ion channels. 8-Bromo-cyclic GMP and sodium nitroprusside antagonized the Ca2+-dependent 86Rb efflux induced by 3 × 10−7M 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 10−7M 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 10−5M methylene blue, the K+-channel-opening activity was unmasked on addition of 10−4M glibenclamide at high concentrations of nicorandil.

This publication has 0 references indexed in Scilit: