1 The effects of racemic cromakalim and the ( + )-3R,4S and ( - )-3S,4R isomers, BRL 38226 and levcromakalim respectively, on the membrane potential of the rat aorta have been determined. In addition, preliminary studies of the effects of BRL 38226 on the contractility of the rat aorta and portal vein have been made. 2 The rat aorta is hyperpolarized by racemic cromakalim at 10 mu M and by levcromakalim at 1 mu M, but is depolarized by BRL 38226 at 1 mu M. 3 In the presence of depolarization with 20 mu M KCl, racemic cromakalim and levcromakalim, but not BRL 38226, reversed the depolarization of the rat aorta. 4 In the presence of hyperpolarization with isoprenaline at 1 mu M or in a CaCl2-free Krebs solution, racemic cromakalim and BRL 38226, but not levcromakalim reversed the hyperpolarization. 5 Glibenclamide at 0.3 and 1 mu M depolarized the rat aorta. Pretreatment with glibenclamide at 1 mu M prevented the hyperpolarizing action of racemic cromakalim but did not alter the depolarizing action of BRL 38226. Pretreatrnent with BRL 38226 at 10 mu M also prevented the hyperpolarizing action of racemic cromakalim. 6 Contractility studies demonstrated that BRL 38226 and glibenclamide have no effect on the resting tone of the rat aorta in normal Krebs solution. However in a CaCl2-free Krebs solution, BRL 38226 and glibenclamide, 0.1-100 mu M, caused small contractions. BRL 38226 and glibenclamide increased the spontaneous contractile activity of the rat portal vein in normal Krebs solution. 7 The present study illustrates that levcromakalim opens the ATP-dependent potassium channels of the rat aorta to cause hyperpolarization. BRL 38226 and glibenclamide produce depolarization and contraction of the rat aorta and increase the contractile activity of the rat portal vein, possibly by blocking the ATP-dependent potassium channels.
