Comparison of the effluxes of 42K+ and 86Rb+ elicited by cromakalim (BRL 34915) in tonic and phasic vascular tissue.
The cromakalim-induced effluxes of 42K+ and 86Rb+ were compared in rat aortic segments and in guinea-pig portal vein. In both vessels, low concentrations of cromakalim (0.1 microM) increased the permeability to 86Rb+ 3-4 times less than that to 42K+; at 10 microM the difference was about a factor of 1.3-2. In rat aorta, the threshold concentration of cromakalim for 42K+ efflux was greater than or equal to 0.03 microM; with 86Rb+ as the tracer ion it was 0.1 microM. At similar concentrations, cromakalim relaxed the tension of aortic segments precontracted with 23 mM KCl (IC50 = 0.06 +/- 0.01 microM). However, no concomitant increase in 42K+ or 86Rb+ efflux could be detected from this stimulated preparation at these concentrations. In guinea-pig portal vein, 42K+ efflux measurements were performed in the presence and absence of the dihydropyridine Ca2+ entry blocker PN 200-110 (isradipine) yielding comparable results. In the presence of PN 200-110, where spontaneous activity and the K+ efflux associated with it were abolished, the threshold concentration of cromakalim for 42K+ efflux was 0.02 microM as compared to 0.06 microM for 86Rb+ efflux. In the absence of PN 200-110, spontaneous activity of the portal vein was inhibited by 70% and 90% at these concentrations. In double isotope experiments, the K+ channel inhibitor tetraethylammonium did not discriminate between the effluxes of 42K+ and 86Rb+ stimulated by cromakalim. It is concluded that in the two vascular tissues examined, cromakalim increased the permeability to 42K+ more than to 86Rb+, the difference being more marked at low cromakalim concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Quast
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Cardiovascular Department, Sandoz Ltd, Basel, Switzerland.
Baumlin
Y
Y
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D006168:Guinea Pigs; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011169:Portal Vein / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D011197:Potassium Radioisotopes; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D012413:Rubidium / Q000378:metabolism*; D012414:Rubidium Radioisotopes
D000959:Antihypertensive Agents; D001578:Benzopyrans; D011197:Potassium Radioisotopes; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D019806:Cromakalim; D012413:Rubidium; D011188:Potassium