COMPARATIVE EFFECTS OF THE POTASSIUM CHANNEL OPENERS CROMAKALIM AND PINACIDIL AND THE CROMAKALIM ANALOG U-89232 ON ISOLATED VASCULAR AND CARDIAC TISSUE

ATP-sensitive potassium (K-ATP(+)) channel openers such as cromakalim and pinacidil exhibit both potent vasodilatory and anti-ischemic prope rties. U-89232, a cyanoguanidine analog of cromakalim, has recently be en found to exhibit myocardial protection during ischemia without alte ring in vivo hemodynamics. We examined the effects of U-89232, cromaka lim and pinacidil in isolated vascular and cardiac tissue and tested w hether glyburide, a K-ATP channel blocker, could antagonize their effe cts. All three compounds produced concentration-dependent relaxation i n isolated vascular segments,with cromakalim being approximately 100-f old more potent than either pinacidil or U-89232. Glyburide completely antagonized the effects of pinacidil but merely blunted the effects o f cromakalim and U-89232. In an isolated rabbit cardiac tissue prepara tion, U-89232 had little effect on maximum tension in cardiac muscle, whereas cromakalim and pinacidil significantly decreased maximum devel oped tension in a concentration-dependent manner. Glyburide effectivel y antagonized the effects of cromakalim and pinacidil in cardiac tissu e. These data suggest that U-89232, although chemically related to cro makalim, possesses activity which is not common to known potassium cha nnel openers.