Comparison of cromakalim-induced relaxation of potassium precontracted rabbit, cat, and rat isolated cerebral arteries

Abstract

The effects of cromakalim were investigated in KCl-precontracted cat, rabbit, and rat isolated cerebral arteries with intact endothelium. Potassium induced contraction of all cerebral arteries studied, but exhibited marked vessel and species variation with no spasm to 20 or 30 mmol/l KCl in the rat basilar artery or 20 mmol/l KCl in the rabbit middle cerebral artery. On sustained tension to 20 mmol/l KCl, cromakalim induced concentration-related relaxation in the rabbit basilar artery and the cat basilar and middle cerebral arteries with Hill coefficients greater than unity. Cromakalim was more potent in the rabbit basilar artery precontracted with 20 or 30 mmol/KCl than in the rabbit middle cerebral artery or the cat basilar or middle cerebral artery. Elevation of the KCl concentration to 50 mmol/l inhibited cromakalim-induced relaxation and produced a decrease in the Hill coefficient. Preincubation of cerebral arteries with glibenclamide (100 nmol/l-1 mumol/l) produced concentration-related inhibition of the cromakalim-induced relaxation in the rabbit basilar, cat basilar, and cat middle cerebral arteries precontracted with 20 mmol/l KCl. The degree of rightward shift of concentration-effect curves by glibenclamide was calculated at the EC25, EC50, and EC75 levels. A good correlation was observed between the shifts at the EC50 and EC75 levels. However, the shift in concentration-effect curves for cromakalim produced at the EC25 level was markedly less than the EC50 or EC75 levels in the presence of 1 mumol/l glibenclamide. The pA2 values for glibenclamide calculated at the EC50 level were 6.6 +/- 0.09, 7.1 +/- 0.1, and 6.5 +/- 0.5 in the rabbit basilar, cat basilar, and cat middle cerebral artery, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)