title: High-salt diet depresses acetylcholine reactivity proximal to NOS activation in cerebral arteries.
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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Francis A
authors.initials: FA
authors.lastname: Sylvester
authors.forename: David W
authors.initials: DW
authors.lastname: Stepp
authors.forename: Jefferson C
authors.initials: JC
authors.lastname: Frisbee
authors.forename: Julian H
authors.initials: JH
authors.lastname: Lombard
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D000090762:Cytochrome P-450 CYP2J2; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010105:Oxygenases / Q000037:antagonists & inhibitors; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D051381:Rats; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000096:biosynthesis; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014226:Triazenes / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D017673:Sodium Chloride, Dietary; D014226:Triazenes; D014665:Vasodilator Agents; D013481:Superoxides; C099612:NOC 9; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D019001:Nitric Oxide Synthase; D000090762:Cytochrome P-450 CYP2J2; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine; D001920:Bradykinin