Ganglionic tyrosine hydroxylase and norepinephrine transporter are decreased by increased sodium chloride in vivo and in vitro.
The present study tested the hypothesis that, in normal male rats, chronic changes in salt intake alter the levels of tyrosine hydroxylase and the norepinephrine transporter in sympathetic ganglia. Increasing dietary salt (from 0.02% to 1%, 4% or 8% NaCl in rat chow) decreased (p<0.05) the mRNA levels of tyrosine hydroxylase and the norepinephrine transporter in the adrenal gland, superior cervical ganglia and celiac ganglia. In addition, tyrosine hydroxylase and norepinephrine transporter protein levels were decreased (p<0.05) in the adrenal gland. To test the hypothesis that NaCl acts directly on postganglionic neurons to suppress the expression of these proteins, it was determined if increases in NaCl concentrations, of a magnitude achieved during increases in dietary salt in vivo, suppress expression of tyrosine hydroxylase and the norepinephrine transporter in cultured sympathetic neurons in vitro. Increased dietary salt increased plasma NaCl concentrations each by up to 4-6 mEq l(-1) (p<0.05), with the greatest increases occurring at night when the rats consume most of their food. In addition, NaCl added to cultured neurons decreased tyrosine hydroxylase and norepinephrine transporter protein and mRNA levels, and norepinephrine uptake; however, the NaCl concentration increases required were 15-30 mEq l(-1). These data suggest that increased dietary salt can influence the activity of the sympathetic nervous system by suppressing the levels of tyrosine hydroxylase and the norepinephrine transporter. While increased NaCl levels can act directly on neurons to suppress these proteins, this action may occur in vivo only in severe pathophysiological states, but not during increases in dietary salt without the synergistic effect of other factors.
Habecker
Beth A
BA
Department of Physiology and Pharmacology, L-334, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA.
Grygielko
Eugene T
ET
Huhtala
Timothy A
TA
Foote
Billy
B
Brooks
Virginia L
VL
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000494:pharmacology*; D017783:Superior Cervical Ganglion / Q000187:drug effects* / Q000378:metabolism; D027981:Symporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493226:Slc6a2 protein, rat; D017673:Sodium Chloride, Dietary; D027981:Symporters; D012965:Sodium Chloride; D014446:Tyrosine 3-Monooxygenase