Li Jianping, Wang Donna H
Department of Medicine, Neuroscience Program, and Cell and Molecular Biology Program, Michigan State University, East Lansing, MI 48824, USA.
J Hypertens. 2007 May;25(5):1065-72. doi: 10.1097/HJH.0b013e3280a8b87d.
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.
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.
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.
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.
确定噻嗪类敏感的氯化钠共转运体（NCC）、钠钾氯共转运体（NKCC2）和上皮钠通道（ENaC）在盐敏感高血压模型大鼠肾脏中的功能及调节机制。
对新生Wistar大鼠进行辣椒素或赋形剂处理。7周龄雄性大鼠接受为期2周的以下处理：赋形剂加正常（Con-NS）或高（Con-HS）钠饮食，以及辣椒素预处理加正常（Cap-NS）或高（Cap-HS）钠饮食。测定平均动脉压（MAP）、肾脏排泄功能，并通过蛋白质印迹法测定蛋白质表达。
与其他组相比，Cap-HS组的MAP升高。三氯噻嗪仅增加了Cap-HS大鼠的尿钠排泄（UNaV）和尿流率（UFR），并降低了其MAP。呋塞米增加了Cap-NS、Con-HS和Cap-HS组的UNaV和UFR，且仅降低了Cap-HS大鼠的MAP。氨氯地平对任何组的UNaV、UFR和MAP均无影响。与Con-NS、Con-HS和Cap-NS大鼠相比，Cap-HS大鼠肾脏中的NCC含量增加，与Con-NS大鼠相比，Cap-NS、Con-HS和Cap-HS组中的NKCC2表达增加。ENaCα亚基表达未发现变化。与Con-HS和Con-NS大鼠相比，Cap-HS和Cap-NS组中辣椒素诱导的肾脏组织降钙素基因相关肽释放减少。
在感觉神经变性加高盐摄入的大鼠肾脏中，NCC以及可能的NKCC2功能上调，但ENaC未上调，这表明感觉神经递质可能调节前者的表达而非后者，这可能是该模型中盐敏感性高血压发生的基础。
