Differential effects of acetylcholine, nitric oxide and levcromakalim on smooth muscle membrane potential and tone in the rabbit basilar artery.
1. Endothelium-dependent hyperpolarization of smooth muscle cells in isolated, pre-contracted segments of rabbit basilar artery in response to acetylcholine (100 microM) was abolished in the presence of glibenclamide (10 microM). 2. Acetylcholine-evoked relaxation was unaffected by either glibenclamide or 65 mM potassium chloride, indicating that the change in membrane potential did not form an essential component of relaxation and that high concentrations of potassium did not inhibit the release or action of endothelium-derived relaxing factor in this vessel. 3. Saturated solutions of nitric oxide (NO) gas in solution (150 microM), which evoked maximal relaxation of arterial segments pre-contracted and depolarized by noradrenaline (10-100 microM), did not alter the membrane potential of either unstimulated or depolarized smooth muscle cells. 4. The potassium channel opener levcromakalim, evoked concentration-dependent relaxation and hyperpolarization in pre-constricted smooth muscle cells. The threshold concentrations for hyperpolarization and relaxation, the EC50 values and the maximally effective concentration of levcromakalim (around 30 nM, 150 nM and 10 microM, respectively) were not significantly different, and both components of the response were inhibited by glibenclamide (10 microM), indicating a close coupling between the two responses. 5. In the presence of 65 mM potassium chloride, the hyperpolarization to levcromakalim was abolished, while a small relaxation (25 +/- 4%) persisted, indicating an additional mechanism for relaxation to this agent. 6. These results show that different mechanisms underlie the relaxant action of potassium channel openers, NO and endothelium-derived factors in cerebral arteries and provide further evidence that in the basilar artery, in contrast to some other vessels, endothelium-dependent hyperpolarization to acetylcholine is not important for smooth muscle relaxation.
Plane
F
F
Department of Physiology and Pharmacology, University of Southampton.
Garland
C J
CJ
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004594:Electrophysiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009569:Nitric Oxide; D011189:Potassium Chloride; D000109:Acetylcholine; D005905:Glyburide; D009638:Norepinephrine