TY - JOUR
T1 - High-salt diet depresses acetylcholine reactivity proximal to NOS activation in cerebral arteries
AU - Sylvester, Francis A.
AU - Stepp, David W.
AU - Frisbee, Jefferson C.
AU - Lombard, Julian H.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - 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 (O2-) production, assessed by dihydroethidine fluorescence, and ACh responses were unaffected by O2- 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 O2- levels, and 3) alteration(s) in ACh signaling are located upstream from NO synthase.
AB - 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 (O2-) production, assessed by dihydroethidine fluorescence, and ACh responses were unaffected by O2- 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 O2- levels, and 3) alteration(s) in ACh signaling are located upstream from NO synthase.
KW - Bradykinin
KW - Cyclooxygenase
KW - Endothelium
KW - Epoxyeicosatrienoic acids
KW - Nitric oxide
KW - Superoxide
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U2 - 10.1152/ajpheart.00127.2002
DO - 10.1152/ajpheart.00127.2002
M3 - Article
C2 - 12063309
AN - SCOPUS:0036299748
VL - 283
SP - H353-H363
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 1 52-1
ER -