title: 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.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Institute of Laboratory Medicine, Lund University, SE-221 85 Lund, Sweden.
authors.forename: D A
authors.initials: DA
authors.lastname: Andersson
authors.forename: P M
authors.initials: PM
authors.lastname: Zygmunt
authors.forename: P
authors.initials: P
authors.lastname: Movahed
authors.forename: T L
authors.initials: TL
authors.lastname: Andersson
authors.forename: E D
authors.initials: ED
authors.lastname: Högestätt
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000473:Alkanes / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001685:Biological Factors / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D003022:Clotrimazole / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006499:Hepatic Artery / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011806:Quinolinium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012414:Rubidium Radioisotopes / Q000378:metabolism; D012604:Scorpion Venoms / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014403:Tubocurarine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C110349:6,10-diaza-3(1,3),8(1,4)dibenzena-1,5(1,4)diquinolinacyclodecaphane; D000473:Alkanes; D001685:Biological Factors; D004791:Enzyme Inhibitors; D007211:Indoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011806:Quinolinium Compounds; D012414:Rubidium Radioisotopes; D012604:Scorpion Venoms; C067410:endothelium-dependent hyperpolarization factor; C056574:leiurotoxin I; D001464:Barium; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D003022:Clotrimazole; D000109:Acetylcholine; D007654:Ketoconazole; D011188:Potassium; D002118:Calcium; D014403:Tubocurarine; C009990:ciclazindol