caa a22 4500 469079797 CHVBK 20180323132946.0 cr unu---uuuuu 170328e19920201xx s 000 0 eng 10.1007/BF00165744 doi (NATIONALLICENCE)springer-10.1007/BF00165744 Differential inhibition by tedisamil (KC 8857) and glibenclamide of the responses to cromakalim and minoxidil sulphate in rat isolated aorta [Elektronische Daten] [Katharine Bray, Ulrich Quast] Summary: The effects of the K+ channel blockers tedisamil and glibenclamide on cromakalim- and minoxidil sulphate-induced 42K+ and 86Rb+ efflux and vasorelaxation in rat aorta, were investigated. In aortic strips preloaded with 42K+ or 86Rb+, cromakalim (1 μmol/l) induced increases in tracer efflux, which were concentration-dependently inhibited by tedisamil with similar potencies (pD2 ≈ 7.3) but different amplitudes (maximum inhibition of 86Rb+ efflux to 0% of control, 42K+ efflux to 10 ± 1%). The 42K+ efflux elicited by a low concentration of cromakalim (100 nmol/l) was, however, fully inhibited by tedisamil. The tracer effluxes induced by minoxidil sulphate were fully inhibited by tedisamil and glibenclamide (300 nM). Cromakalim and minoxidil sulphate, produced a concentration-dependent inhibition of noradrenaline (100 nmol/l)-induced tone, with pD2 values of ≈7.3. Tedisamil (300 nmol/1) and glibenclamide (300 nmol/l), which inhibited cromakalim- and minoxidil sulphate-induced 42K+ and 86Rb+ efflux by ≥80%, produced 2-fold and 40-fold shifts in the concentration-relaxation curve for cromakalim, and 3.5-fold and 2200-fold shifts in the concentration-relaxation curve for minoxidil sulphate, respectively. Similar shifts of the cromakalim concentration-relaxation curve in the presence of tedisamil and glibenclamide were also observed when the tissues were precontracted with potassium chloride (25 mmol/l). The results show that tedisamil and glibenclamide inhibit the cromakalim- and minoxidil sulphate-induced tracer effluxes with similar potencies whereas they differ greatly in their ability to inhibit the vasorelaxant effects of the two K+ channel openers. This suggests that the opening of 42K+/86Rb+ permeable K+ channels in the plasma membrane cannot fully explain the vasorelaxant effects of the two drugs. The mechanism(s) of vasorelaxation of cromakalim and minoxidil sulphate, which is not due to the opening of plasmalemmal K+ channels, is sensitive to inhibition by glibenclamide but comparatively insensitive to inhibition by tedisamil. Springer-Verlag, 1992 Tedisamil nationallicence Glibenclamide nationallicence Cromakalim nationallicence Minoxidil sulphate nationallicence Rat aorta nationallicence Bray Katharine Cardiovascular Department, Preclinical Research, Sandoz Pharma Ltd., CH-4002, Basel, Switzerland aut Quast Ulrich Cardiovascular Department, Preclinical Research, Sandoz Pharma Ltd., CH-4002, Basel, Switzerland aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/2(1992-02-01), 244-250 0028-1298 345:2<244 1992 345 210 https://doi.org/10.1007/BF00165744 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00165744 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bray Katharine Cardiovascular Department, Preclinical Research, Sandoz Pharma Ltd., CH-4002, Basel, Switzerland aut NATIONALLICENCE 700 1- Quast Ulrich Cardiovascular Department, Preclinical Research, Sandoz Pharma Ltd., CH-4002, Basel, Switzerland aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/2(1992-02-01), 244-250 0028-1298 345:2<244 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer