Barium decreases endothelium-dependent smooth muscle responses to transient but not to more prolonged acetylcholine applications.
The influence of inhibiting the inward rectifier and Na/K pump on endothelium-dependent hyperpolarizations in smooth muscle cells of the mesenteric artery was investigated. Membrane potential was measured with microelectrodes, and the influence of low concentrations of Ba2+ (30 microM) and of high concentrations of ouabain (0.5 mM) on smooth muscle hyperpolarization elicited by prolonged or by transient exposure to acetylcholine (ACh, 3x10(-7) M) was assessed in the continuous presence of NG-nitro-L-arginine (100 microM) and indomethacin (50 microM). Pre-exposure to Ba2+ did not inhibit the magnitude of smooth muscle cell hyperpolarization induced by ACh superfusion, but significantly slowed its onset and time course. The membrane potential response to transient ACh applications, however, was impaired. After combined Ba2+ and ouabain pre-exposure, peak hyperpolarizations to ACh superfusion were somewhat decreased but not abolished. In addition, 4-5 mM increases of the extracellular K+ concentration consistently depolarized smooth muscle cells. These findings argue against the idea that smooth muscle inward rectifier K+ channels and Na/K pumping play a role in the ACh-induced endothelium-dependent hyperpolarization of this preparation. Moreover, the slowing of smooth muscle membrane hyperpolarization by Ba2+ is discussed in terms of the influence of this ion on the release of hyperpolarizing factor.
Vanheel
B
B
Department of Physiology and Physiopathology, University of Gent, Belgium. Bert.Vanheel@rug.ac.be
Van de Voorde
J
J
D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D001464:Barium; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine; D007213:Indomethacin