Effect of some potassium channel blockers on contractile responses of the rabbit aorta.
Contractile responses of rabbit aortic rings to KCl or angiotensin II (AII) were investigated in the presence of five compounds known to block K+ channels. Tetraethylammonium (3 and 10 mM), 3,4-diaminopyridine (0.3 and 1 mM), and a charybdotoxin-like toxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (3-30 ng ml-1), augmented contractions due to low but not high KCl concentrations and increased the maximum tissue response to AII. This latter augmentation could be reduced (but not fully inhibited) by the calcium entry blocker PN 200-100 (100 nM), implicating an influx of extracellular calcium in the response. 3,4-Diaminopyridine (1 mM) and the scorpion toxin additionally increased the resting tension of the aortic rings, an effect not observed with tetraethylammonium at concentrations up to 10 mM. Apamin and toxin I (both 1 microM) failed to modify KCl or AII contractions of the aorta. In all cases, aortic rings denuded of endothelium gave essentially the same results as rings having an intact endothelium. These results are discussed in relation to the possible types of K+ channels involved in modulating the tone of this blood vessel during hormonal stimulation.
Cook
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NS
Cardiovascular Department, Preclinical Research, Sandoz Ltd., Basel, Switzerland.
D015761:4-Aminopyridine / Q000031:analogs & derivatives*; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001030:Apamin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D017275:Isradipine; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D012604:Scorpion Venoms / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000631:Aminopyridines; D002121:Calcium Channel Blockers; D010069:Oxadiazoles; D015221:Potassium Channels; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D001030:Apamin; D015761:4-Aminopyridine; D000077770:Amifampridine; D017275:Isradipine