Inhibitors of the cytochrome P450-mono-oxygenase and endothelium-dependent hyperpolarizations in the guinea-pig isolated carotid artery.
1. Transmembrane potentials were recorded from isolated carotid arteries of the guinea-pig superfused with modified Krebs-Ringer bicarbonate solution. Smooth muscle cells were impaled with sharp intracellular microelectrodes. 2. Acetylcholine (1 microM) induced an endothelium-dependent hyperpolarization (14.3 +/- 2.8 mV, n = 6) which was not affected (15.1 +/- 1.1 mV, n = 35) by inhibitors of cyclo-oxygenase (indomethacin, 5 microM) and nitric oxide synthase (N omega nitro-L-arginine: L-NOARG, 100 microM). 3. The hyperpolarization produced by acetylcholine was abolished in the presence of elevated potassium (35 mM) in the superfusing physiological saline solution. 4. The acetylcholine-induced hyperpolarization was not affected by the inhibitors of cytochrome P450 mono-oxygenases, SKF525a (10 and 100 microM, 13.9 +/ 2.2 and 15.3 +/- 4.6 mV), metyrapone (100 microM, 13.1 +/- 1.9 mV), clotrimazole (100 microM, 13.5 +/- 2.7 mV), 17-octadecynoic acid (5 microM, 16.5 +/- 1.9 mV), methoxsalen (10 microM, 15.3 +/- 1.6 mV), the inhibitor of phospholipase A2 quinacrine (10 microM 12.8 +/- 2.5 mV) and the non specific lipoxygenases/cyclo-oxygenases/cytochrome P450 inhibitor, eicosatetraynoic acid (50 microM, 15.0 +/- 2.2 mV). However, the muscarinic antagonist, atropine (100 nM), abolished the hyperpolarization. 5. These results suggest that in guinea-pig carotid artery, the metabolism of arachidonic acid, either through cyclo-oxygenase, lipoxygenase or cytochrome p450 mono-oxygenase, is not involved in acetylcholine-induced endothelium-dependent hyperpolarizations.
Corriu
C
C
Department de Pneumologie, Institut de Recherches Servier 11, Suresnes, France.
Félétou
M
M
Canet
E
E
Vanhoutte
P M
PM
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D010105:Oxygenases / Q000037:antagonists & inhibitors*
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D010105:Oxygenases