Zhu Yi, Wang Youping, Wang Donna H
Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA.
Hypertension. 2005 Oct;46(4):992-7. doi: 10.1161/01.HYP.0000174603.27383.67. Epub 2005 Aug 8.
To test the hypothesis that activation of the vanilloid receptor 1 (VR1) expressed in sensory nerves innervating the renal pelvis leads to diuresis and natriuresis, a selective VR1 receptor agonist, capsaicin (2.4 nmol), or vehicle was perfused intravenously or into the left renal pelvis of anesthetized rats at a rate without changing renal perfusion pressure. Mean arterial pressure was not altered by capsaicin administered intravenously or into the renal pelvis. Capsaicin perfusion into the left renal pelvis but not intravenously caused significant increases in urine flow rate and urinary sodium excretion bilaterally in a dose-dependent manner, which were abolished by capsazepine, a selective VR1 receptor antagonist, given ipsilaterally to the renal pelvis or by ipsilateral renal denervation. Capsaicin given intravenously or into the left renal pelvis increased plasma calcitonin gene-related peptide levels to the same extent. Increased plasma calcitonin gene-related peptide levels induced by capsaicin (68.9+/-2.8 pg/mL) perfusion into the renal pelvis was prevented either by capsazepine (22.5+/-10.1 pg/mL) given ipsilaterally into the renal pelvis or by ipsilateral renal denervation (25.9+/-2.3 pg/mL). Taken together, our data show that unilateral activation of VR1-positive sensory nerves innervating the renal pelvis leads to bilateral diuresis and natriuresis via a mechanism that is independent of plasma calcitonin gene-related peptide levels. These data suggest that VR1-positive sensory nerves in the kidney enhance renal excretory function, a mechanism that may be critically involved in sodium and fluid homeostasis.
为了验证支配肾盂的感觉神经中表达的香草酸受体1（VR1）激活会导致利尿和利钠这一假说，将选择性VR1受体激动剂辣椒素（2.4 nmol）或赋形剂以不改变肾灌注压的速率静脉内灌注或注入麻醉大鼠的左肾盂。静脉内或肾盂内给予辣椒素均未改变平均动脉压。向左侧肾盂而非静脉内灌注辣椒素会以剂量依赖性方式双侧显著增加尿流率和尿钠排泄，而给予肾盂同侧的选择性VR1受体拮抗剂辣椒平或进行同侧肾去神经支配后，这些作用消失。静脉内或向左侧肾盂给予辣椒素会使血浆降钙素基因相关肽水平升高至相同程度。向肾盂灌注辣椒素（68.9±2.8 pg/mL）所诱导的血浆降钙素基因相关肽水平升高，可通过在肾盂同侧给予辣椒平（22.5±10.1 pg/mL）或进行同侧肾去神经支配（25.9±2.3 pg/mL）来预防。综上所述，我们的数据表明，支配肾盂的VR1阳性感觉神经的单侧激活通过一种独立于血浆降钙素基因相关肽水平的机制导致双侧利尿和利钠。这些数据提示，肾脏中的VR1阳性感觉神经增强了肾脏排泄功能，这一机制可能在钠和液体稳态中起关键作用。
