Turban S, Beutler K T, Morris R G, Masilamani S, Fenton R A, Knepper M A, Packer R K
Laboratory of Kidney and Electrolyte Metabolism, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kidney Int. 2006 Aug;70(4):660-8. doi: 10.1038/sj.ki.5001571.
In the proximal tubule, angiotensin II (Ang-II) regulates HCO(-)(3) reabsorption and H+ secretion by binding the type 1 Ang-II (AT1) receptor, stimulating Na(+)/HCO(-)(3) cotransport and Na(+)/H(+) exchange. Studies were carried out to determine if long-term changes in Ang-II receptor occupation alter the abundance of the basolateral Na(+)/HCO(-)(3) cotransporter (NBC1) or the apical membrane type 3 Na(+)/H(+) exchanger (NHE3). In the first set of experiments, rats eating a low-sodium diet were infused with the AT1 blocker, candesartan, or vehicle. In the second, lisinopril-infused rats were infused with either Ang II or vehicle. Transporter abundances were determined in whole kidney homogenates (WKH) and in brush border membrane (BBM) preparations by semiquantitative immunoblotting. Tissue distribution of transporters was assessed by immunocytochemistry. Blockade of the AT1 receptor by candesartan caused decreased abundance of NBC1 in WKH (59 +/- 9% of control; P<0.05) and Ang-II infusion increased abundance (130 +/- 7% of control; P<0.05). Changes in NBC1 in response to candesartan were confirmed immunohistochemically. Neither candesartan nor Ang II infusion affected the abundance of NHE3 in WKH or cortical homogenates. Candesartan decreased type 2 sodium-phosphate cotransporter abundance in both WKH (52 +/- 7% of control; P<0.05) and BBM (32 +/- 7% of control; P<0.05). Serum bicarbonate was decreased by candesartan and increased by Ang-II. Candesartan also decreased urinary ammonium excretion (P<0.05). The long-term effects of Ang-II in the proximal tubule may be mediated in part by regulation of NBC1 abundance, modifying bicarbonate reabsorption.
在近端小管中，血管紧张素II（Ang-II）通过与1型Ang-II（AT1）受体结合来调节HCO(-)(3)的重吸收和H+分泌，刺激Na(+)/HCO(-)(3)协同转运和Na(+)/H(+)交换。本研究旨在确定长期改变Ang-II受体占有率是否会改变基底外侧Na(+)/HCO(-)(3)协同转运体（NBC1）或顶端膜3型Na(+)/H(+)交换体（NHE3）的丰度。在第一组实验中，给食用低钠饮食的大鼠输注AT1阻滞剂坎地沙坦或赋形剂。在第二组实验中，给输注赖诺普利的大鼠输注Ang II或赋形剂。通过半定量免疫印迹法测定全肾匀浆（WKH）和刷状缘膜（BBM）制剂中的转运体丰度。通过免疫细胞化学评估转运体的组织分布。坎地沙坦阻断AT1受体导致WKH中NBC1丰度降低（为对照的59±9%；P<0.05），而输注Ang-II则增加丰度（为对照的130±7%；P<0.05）。免疫组织化学证实了坎地沙坦引起的NBC1变化。坎地沙坦和Ang II输注均未影响WKH或皮质匀浆中NHE3的丰度。坎地沙坦降低了WKH（为对照的52±7%；P<0.05）和BBM（为对照的32±7%；P<0.05）中2型钠-磷酸盐协同转运体的丰度。坎地沙坦使血清碳酸氢盐降低，而Ang-II使其升高。坎地沙坦还降低了尿铵排泄（P<0.05）。Ang-II在近端小管中的长期作用可能部分是通过调节NBC1丰度来介导的，从而改变碳酸氢盐的重吸收。
