Comparison of effects of cromakalim and pinacidil on mechanical activity and 86Rb efflux in dog coronary arteries.
Effects of two K+ channel openers, cromakalim and pinacidil, on mechanical activity and on 86Rb efflux were compared in strips of dog coronary arteries. Cromakalim and pinacidil produced the relaxation in 20.9 mM K(+)-contracted strips with a pD2 of 6.53 and 5.95, respectively. In 65.9 mM K(+)-contracted strips, high concentrations of pinacidil, but not cromakalim, produced relaxation. Ca+(+)-induced contractions in 80 mM K(+)-depolarized strips were also inhibited by pinacidil but not by cromakalim. Glibenclamide, a blocker of ATP-regulated K+ (KATP) channels, competitively antagonized the relaxant responses to cromakalim with a pA2 value of 7.62. However, the antagonism by glibenclamide of the relaxant responses to pinacidil was not a typical competitive type, suggesting the contribution of other effects than the KATP channel opening activity to the relaxant effects of pinacidil. In resting strips preloaded with 86Rb, cromakalim and pinacidil increased the basal 86Rb efflux in a dose-dependent manner. The increase in the 86Rb efflux induced by cromakalim was greater than that by pinacidil. When the effects of cromakalim and pinacidil on the 86Rb efflux were determined in the 20.9 or 65.9 mM K(+)-contracted strips, both drugs increased the 86Rb efflux. Under the same conditions nifedipine, a Ca(+)+ channel blocker, produced the relaxation that is accompanied by the decrease in 86Rb efflux. The increase in the 86Rb efflux induced by cromakalim was much greater than that by pinacidil.(ABSTRACT TRUNCATED AT 250 WORDS)
Masuzawa
K
K
Department of Pharmacology, Nagoya City University Medical School, Japan.
Asano
M
M
Matsuda
T
T
Imaizumi
Y
Y
Watanabe
M
M
D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D019806:Cromakalim; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012414:Rubidium Radioisotopes; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001578:Benzopyrans; D015220:Calcium Channels; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D014665:Vasodilator Agents; D019806:Cromakalim; D020110:Pinacidil; D005905:Glyburide