Comparison of the relaxing effects of cicletanine and cromakalim on vascular smooth muscle.

Cicletanine inhibited the spontaneous activity of portal vein preparations (rat, guinea pig, and rabbit) and that produced by norepinephrine or an increase in external K+ concentration to 20 mmol/L in seven types of vascular smooth muscle preparation (portal vein of rat, guinea pig, and rabbit; aorta of rat and guinea pig; and iliac artery and ear artery of rabbit). The cicletanine EC50 was approximately 10(-4) mol/L. Contractions produced by K+ = 80 mmol/L were also inhibited by cicletanine in most preparations. Only in aortic strips of rat and guinea pig and in rabbit iliac artery were the concentration-response relationships for cicletanine shifted to the right, yielding EC50 values of approximately 3 x 10(-4) mol/L. In contrast, the inhibitory effects of the potassium channel opener cromakalim (BRL 34915) were completely abolished during K+ = 80 mmol/L treatment in all preparations. The inhibitory effect of cromakalim under the other test conditions (above) was completely antagonized by application of glibenclamide, 10(-5) mol/L, whereas this treatment had only negligible effects on cicletanine inhibition in most preparations. The results indicate that a potassium channel opening effect does not contribute significantly to the inhibitory effect of cicletanine on vascular smooth muscle.