| Effects of volatile anesthetics on acetylcholine-induced relaxation in the rabbit mesenteric resistance artery. | |
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MedLine Citation:
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PMID: 7832300 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Vascular endothelium plays an important role in the regulation of vascular tone. Volatile anesthetics have been shown to attenuate endothelium-mediated relaxation in conductance arteries, such as aorta. However, significant differences in volatile anesthetic pharmacology between these large vessels and the small vessels that regulate systemic vascular resistance and blood flow have been documented, yet little is known about volatile anesthetic action on endothelial function in resistance arteries. Furthermore, endothelium-dependent relaxation mediated by factors other than endothelium-derived relaxing factor (EDRF) has recently been recognized, and there is no information available regarding volatile anesthetic action on non-EDRF-mediated endothelium-dependent relaxation. METHODS: Employing isometric tension recording and microelectrode methods, the authors first characterized the endothelium-dependent relaxing and hyperpolarizing actions of acetylcholine (ACh) in rabbit small mesenteric arteries, and tested the sensitivities of these actions to EDRF pathway inhibitors and K+ channel blockers. They then examined the effects of the volatile anesthetics isoflurane, enflurane, and sevoflurane on ACh-induced endothelium-dependent relaxation that was sensitive to EDRF inhibitors and that which was resistant to the EDRF inhibitors but sensitive to blockers of ACh-induced hyperpolarization. The effects of the volatile anesthetics on endothelium-independent sodium nitroprusside (SNP)-induced relaxation were also studied. RESULTS: Acetylcholine concentration-dependently caused both endothelium-dependent relaxation and hyperpolarization of vascular smooth muscle. The relaxation elicited by low concentrations of ACh (< or = 0.1 microM) was almost completely abolished by the EDRF inhibitors NG-nitro-L-arginine (LNNA), oxyhemoglobin (HbO2), and methylene blue (MB). The relaxation elicited by higher concentrations of ACh (> or = 0.3 microM) was only attenuated by the EDRF inhibitors. The remaining relaxation, as well as the ACh-induced hyperpolarization that was also resistant to EDRF inhibitors, were both specifically blocked by tetraethylammonium (TEA > or = 10 mM). Sodium nitroprusside, a NO donor, produced dose-dependent relaxation, but not hyperpolarization, in the endothelium-denuded (E[-]) strips, and the relaxation was inhibited by MB and HbO2, but not TEA (> or = 10 mM). One MAC isoflurane, enflurane, and sevoflurane inhibited both ACh relaxation that was sensitive to the EDRF inhibitors and the ACh relaxation resistant to the EDRF inhibitors and sensitive to TEA, but not SNP relaxation (in the E[-] strips). An additional finding was that the anesthetics all significantly inhibited norepinephrine (NE) contractions in the presence and absence of the endothelium or after exposure to the EDRF inhibitors. CONCLUSIONS: The results confirm that ACh has a hyperpolarizing action in rabbit small mesenteric resistance arteries that is independent of EDRF inhibitors but blocked by the K+ channel blocker TEA. The ACh relaxation in these resistance arteries thus appears to consist of distinct EDRF-mediated and hyperpolarization-mediated components. Isoflurane, enflurane, and sevoflurane inhibited both components of the ACh-induced relaxation in these small arteries, indicating a more global depression of endothelial function or ACh signaling in endothelial cells, rather than a specific effect on the EDRF pathway. All these anesthetics exerted vasodilating action in the presence of NE, the primary neurotransmitter of the sympathetic nervous system, which plays a major role in maintaining vasomotor tone in vivo. This strongly indicates that the vasodilating action of these anesthetics probably dominates over their inhibitory action on the EDRF pathway and, presumably, contributes to their known hypotensive effects in vivo. Finally, the vasodilating action of these anesthetics is, at least in part, independent from endothelium. |
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Authors:
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T Akata; M Nakashima; K Kodama; W A Boyle; S Takahashi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anesthesiology Volume: 82 ISSN: 0003-3022 ISO Abbreviation: Anesthesiology Publication Date: 1995 Jan |
Date Detail:
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Created Date: 1995-02-17 Completed Date: 1995-02-17 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 188-204 Citation Subset: AIM; IM |
Affiliation:
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Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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pharmacology* Anesthetics, Inhalation / pharmacology* Animals Electrophysiology Enflurane / pharmacology Ethers / pharmacology Isoflurane / pharmacology Male Membrane Potentials / drug effects Mesenteric Arteries / drug effects* Methyl Ethers* Muscle Relaxation / drug effects* Muscle, Smooth, Vascular / drug effects*, physiology Nitric Oxide / antagonists & inhibitors, metabolism Nitroprusside / pharmacology Norepinephrine / antagonists & inhibitors Rabbits |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Inhalation; 0/Ethers; 0/Methyl Ethers; 10102-43-9/Nitric Oxide; 13838-16-9/Enflurane; 15078-28-1/Nitroprusside; 26675-46-7/Isoflurane; 28523-86-6/sevoflurane; 51-41-2/Norepinephrine; 51-84-3/Acetylcholine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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