Effects of inhibitors of small- and intermediate-conductance calcium-activated potassium channels, inwardly-rectifying potassium channels and Na(+)/K(+) ATPase on EDHF relaxations in the rat hepatic artery
| Autor: | D A, Andersson, P M, Zygmunt, P, Movahed, T L, Andersson, E D, Högestätt |
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| Rok vydání: | 2000 |
| Předmět: |
Erythrocytes
Indoles Potassium Channels Scorpion Venoms Tubocurarine In Vitro Techniques Rats Sprague-Dawley Biological Factors Hepatic Artery Alkanes Potassium Channel Blockers Animals Humans Clotrimazole Enzyme Inhibitors Ouabain Dose-Response Relationship Drug Quinolinium Compounds Electric Conductivity Acetylcholine Rats Vasodilation Ketoconazole Barium Papers cardiovascular system Potassium Calcium Female Sodium-Potassium-Exchanging ATPase Rubidium Radioisotopes |
| Zdroj: | British journal of pharmacology. 129(7) |
| ISSN: | 0007-1188 |
| Popis: | 1. In the rat hepatic artery, the SK(Ca) inhibitors UCL 1684 (300 nM) completely blocked, and scyllatoxin (1 microM) and d-tubocurarine (100 microM) partially inhibited EDHF relaxations when each of them was combined with charybdotoxin (300 nM). 2. The IK(Ca) inhibitors clotrimazole (3 microM) and 2-chlorophenyl-bisphenyl-methanol (3 microM) strongly depressed EDHF relaxations when each of them was combined with apamin (300 nM). The cytochrome P450 mono-oxygenase inhibitor ketoconazole (10 microM) had no effect in the presence of apamin. 3. Ciclazindol (10 microM), which abolishes EDHF relaxations in the presence of apamin, almost completely prevented the calcium ionophore (A23187) stimulated (86)Rb(+) influx via the Gardos channel (IK(Ca)) in human erythrocytes. 4. The Na(+)/K(+) ATPase inhibitor ouabain (500 microM) and the K(IR) blocker Ba(2+) (30 microM) neither alone nor in combination inhibited EDHF relaxations. Ba(2+) was also without effect in the presence of either apamin or charybdotoxin. 5. In contrast to EDHF, an increase in extracellular [K(+)] from 4.6 mM to 9.6, 14.6 and 19.6 mM inconsistently relaxed arteries. In K(+)-free physiological salt solution, re-admission of K(+) always caused complete and sustained relaxations which were abolished by ouabain but unaffected by Ba(2+). 6. The present study provides pharmacological evidence for the involvement of SK(Ca) and IK(Ca) in the action of EDHF in the rat hepatic artery. Our results are not consistent with the idea that EDHF is K(+) activating Na(+)/K(+) ATPase and K(IR) in this blood vessel. |
| Databáze: | OpenAIRE |
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