Function and regulation of epithelial sodium transporters in the kidney of a salt-sensitive hypertensive rat model.
OBJECTIVE
To determine the function and regulation of thiazide-sensitive NaCl co-transporters (NCC), NaK2Cl co-transporters (NKCC2), and epithelial sodium channels (ENaC) in the kidneys of a salt-sensitive hypertensive model.


METHODS
Neonatal Wistar rats were treated with capsaicin or vehicle. Seven-week-old male rats were treated for 2 weeks with: vehicle plus a normal (Con-NS) or high (Con-HS) sodium diet, and capsaicin pretreatment plus a normal (Cap-NS) or high (Cap-HS) sodium diet. Mean arterial pressure (MAP), renal excretory function, and protein expression determined by western blot were performed.


RESULTS
MAP was increased in Cap-HS compared with other groups. Trichlormethiazide increased urine sodium excretion (UNaV) and urine flow rate (UFR) and decreased MAP in Cap-HS rats only. Furosemide increased UNaV and UFR in Cap-NS, Con-HS and Cap-HS, and decreased MAP in Cap-HS rats only. Amiloride had no effect on UNaV, UFR and MAP in any group. Renal NCC contents were increased in Cap-HS compared with Con-NS, Con-HS and Cap-NS rats, and NKCC2 expression was increased in Cap-NS, Con-HS and Cap-HS compared with Con-NS rats. No change was found in ENaC alpha subunit expression. The capsaicin-induced release of calcitonin gene-related peptide from renal tissues was decreased in Cap-HS and Cap-NS compared with Con-HS and Con-NS rats.


CONCLUSIONS
NCC and possibly NKCC2, but not ENaC, were functionally upregulated in the kidneys of rats subjected to sensory nerve degeneration plus high salt intake, suggesting that sensory neurotransmitters may regulate the expression of the former but not the latter, which may underlie the development of salt-sensitive hypertension in this model.
Li
Jianping
J
Department of Medicine, Neuroscience Program, and Cell and Molecular Biology Program, Michigan State University, East Lansing, MI 48824, USA.
Wang
Donna H
DH
D000818:Animals; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000378:metabolism*; D011984:Sensory Receptor Cells; D049992:Sodium Chloride Symporters / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D064466:Solute Carrier Family 12, Member 1; D015854:Up-Regulation; D014867:Water / Q000378:metabolism
D053503:Epithelial Sodium Channels; D011955:Receptors, Drug; C578716:Slc12a1 protein, rat; D049992:Sodium Chloride Symporters; D017673:Sodium Chloride, Dietary; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; C064415:thiazide receptor; D014867:Water