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

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Summary

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 μmol/1) 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 EC50 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 μmol/1 glibenclamide. The pA 2 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. The slope of the Schild regression for the inhibitory effect of glibenclamide in the rabbit basilar artery was significantly greater than unity but did not differ from unity in cat cerebral arteries. Glibenclamide (1 μmol/l) produced a similar degree of inhibition of the cromakalim-induced relaxation in the 30 mmol/l KCl precontracted rabbit middle cerebral artery and in the rabbit basilar artery exposed to 20 mmol/l KCl. In contrast, tolbutamide 10 μmol/l was essentially inactive against the cromakalim-induced relaxation in all vessels studied. It is concluded that cromakalim produces concentration-dependent relaxations of rabbit and cat isolated cerebral arteries by a mechanism that is similar to that identified in peripheral vasculature and visceral smooth muscle. In this study we were unable to demonstrate effects of cromakalim on the KCl precontracted rat basilar artery, possibly due to the low sensitivity of this preparation to KCl.

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  1. Physiologisches Institut, Universität München, Pettenkoferstrasse 12, W-8000, München 2, Germany

    Andrew A. Parsons, Ernst Ksoll, Jan R. L. Mackert, Lothar Schilling & Michael Wahl

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  1. Andrew A. Parsons
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  2. Ernst Ksoll
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Parsons, A.A., Ksoll, E., Mackert, J.R.L. et al. Comparison of cromakalim-induced relaxation of potassium precontracted rabbit, cat, and rat isolated cerebral arteries. Naunyn-Schmiedeberg's Arch Pharmacol 343, 384–392 (1991). https://doi.org/10.1007/BF00179043

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