Characteristics of KRN2391, a novel vasodilator, compared with those of cromakalim, pinacidil and nifedipine in rat aorta

Abstract

The characteristics of KRN2391, a novel vasodilator, were studied in rat isolated aorta. The effects of KRN2391, cromakalim, pinacidil and nifedipine on the contractions induced by 20, 40 and 80 mM K+ and by 10(-7) M norepinephrine (NE) were measured first. KRN2391, cromakalim and pinacidil selectively inhibited the contractions induced by 20 mM K+ and NE rather than those induced by high concentrations of K+. Nifedipine could not completely inhibit the NE-induced contractions. The vasorelaxant effect of KRN2391 was inhibited by K+ channel blockers and guanylate cyclase inhibitors. KRN2391, cromakalim and pinacidil increased the 86Rb efflux rate coefficient. Thus, KRN2391 exhibits a vasodilator profile similar to that of the K+ channel openers and induces an increase in 86Rb efflux. It is suggested that opening of the membrane K+ channels may be partly involved in the vasorelaxant mechanism of KRN2391.