Li Jianping, Wang Donna H
B 316 Clinical Center, Department of Medicine, Michigan State University, East Lansing, MI 48824, USA.
Exp Physiol. 2008 Aug;93(8):945-53. doi: 10.1113/expphysiol.2008.042036. Epub 2008 Apr 10.
This study tests the hypothesis that dysfunction of transient receptor potential vanilloid type 1 (TRPV1) channels occurs and contributes to the decrease in the glomerular filtration rate (GFR) and sodium/water excretion in Dahl salt-sensitive hypertensive rats. Recirculating Krebs-Henseleit buffer added with inulin was perfused at a constant flow in the isolated kidneys of Dahl salt-sensitive (DS) or Dahl salt-resistant (DR) rats fed a high-salt (HS) or low-salt (LS) diet for 3 weeks. Perfusion pressures (PP) were pre-adjusted to three levels ( approximately 100, approximately 150 or approximately 190 mmHg) with or without phenylephrine. Capsaicin, a selective TRPV1 agonist, in the presence or absence of capsazepine, a selective TRPV1 antagonist, was perfused. Basal GFR, urine flow rate (UFR) and Na(+) excretion (U(Na)V) were significantly lower in DS-HS than in DR-HS, DS-LS and DR-LS rats. Capsaicin caused pressure-dependent decreases in PP and increases in GFR, UFR and U(Na)V in all groups, with less magnitude of decreases in PP and increases in GFR, UFR and U(Na)V in DS-HS than in DR-HS, DS-LS and DR-LS rats. Capsazepine completely blocked the effect of capsaicin on PP, GFR, UFR and U(Na)V in all groups. Thus, these results show that TRPV1 function is impaired in the kidney of DS rats fed a high-salt diet, which may contribute to the decrease in GFR and renal excretory function in DS rats in the face of salt challenge.
瞬时受体电位香草酸亚型1（TRPV1）通道功能障碍会发生，并导致 Dahl 盐敏感型高血压大鼠的肾小球滤过率（GFR）降低以及钠/水排泄减少。将添加了菊粉的 Krebs-Henseleit 缓冲液以恒定流量灌注到喂食高盐（HS）或低盐（LS）饮食3周的 Dahl 盐敏感（DS）或 Dahl 盐抵抗（DR）大鼠的离体肾脏中。灌注压力（PP）在有或没有去氧肾上腺素的情况下预先调节至三个水平（约100、约150或约190 mmHg）。在有或没有选择性TRPV1拮抗剂辣椒素的情况下，灌注选择性TRPV1激动剂辣椒素。DS-HS大鼠的基础GFR、尿流率（UFR）和钠排泄量（U(Na)V）显著低于DR-HS、DS-LS和DR-LS大鼠。辣椒素导致所有组的PP呈压力依赖性降低，GFR、UFR和U(Na)V升高，与DR-HS、DS-LS和DR-LS大鼠相比，DS-HS大鼠的PP降低幅度和GFR、UFR及U(Na)V升高幅度较小。辣椒素完全阻断了辣椒素对所有组的PP、GFR、UFR和U(Na)V的作用。因此，这些结果表明，喂食高盐饮食的DS大鼠肾脏中TRPV1功能受损，这可能导致DS大鼠在面对盐挑战时GFR和肾脏排泄功能降低。
