Abstract
Rats were fed a low-salt (LS; 0.4% NaCl) or high-salt (HS; 4.0% NaCl) diet for 3 days, and the responses of isolated cerebral arteries to acetylcholine (ACh), the nitric oxide (NO)-dependent dilator bradykinin, and the NO donor 6-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-hex-anamine (NOC-9) were determined. ACh-induced vasodilation and NO release, assessed with the fluorescent NO indicator 4,5-diaminofluorescein (DAF-2) diacetate, were eliminated with the HS diet. Inhibition of cyclooxygenase, cytochrome P-450 epoxygenase, and acetylcholinesterase did not alter ACh responses. Bradykinin and NOC-9 caused a similar dilation in cerebral arteries of all groups. Arteries from animals on LS or HS diets exhibited similar levels of basal superoxide (O(2)(-)) production, assessed by dihydroethidine fluorescence, and ACh responses were unaffected by O(2)(-) scavengers. Muscarinic type 3 receptor expression was unaffected by dietary salt intake. These results indicate that 1) a HS diet attenuates ACh reactivity in cerebral arteries by inhibiting NO release, 2) this attenuation is not due to production of a cyclooxygenase-derived vasoconstrictor or elevated O(2)(-) levels, and 3) alteration(s) in ACh signaling are located upstream from NO synthase.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholine / pharmacology*
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Animals
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Bradykinin / pharmacology
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Cerebral Arteries / drug effects*
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Cerebral Arteries / physiology
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Cholinesterase Inhibitors / pharmacology
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Cytochrome P-450 CYP2J2
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Cytochrome P-450 Enzyme Inhibitors
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Cytochrome P-450 Enzyme System
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Fluorescent Dyes
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Free Radical Scavengers / pharmacology
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In Vitro Techniques
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Male
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Nitric Oxide Donors / pharmacology
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / metabolism*
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Oxygenases / antagonists & inhibitors
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Prostaglandin-Endoperoxide Synthases / drug effects
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Rats
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Receptor, Muscarinic M3
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Receptors, Muscarinic / biosynthesis
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Sodium Chloride, Dietary / pharmacology*
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Superoxides / metabolism
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Triazenes / pharmacology
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Vasodilation / drug effects
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Vasodilation / physiology
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Vasodilator Agents / pharmacology*
Substances
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Cholinesterase Inhibitors
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Cytochrome P-450 Enzyme Inhibitors
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Enzyme Inhibitors
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Fluorescent Dyes
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Free Radical Scavengers
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Nitric Oxide Donors
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Receptor, Muscarinic M3
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Receptors, Muscarinic
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Sodium Chloride, Dietary
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Triazenes
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Vasodilator Agents
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Superoxides
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NOC 9
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Cytochrome P-450 Enzyme System
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Oxygenases
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Nitric Oxide Synthase
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Cytochrome P-450 CYP2J2
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Prostaglandin-Endoperoxide Synthases
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Acetylcholine
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Bradykinin