Loss of renal medullary endothelin B receptor function during salt deprivation is regulated by angiotensin II
Loss of renal medullary endothelin B receptor function during salt deprivation is regulated by angiotensin II
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DOI：
10.1152/ajprenal.00213.2012
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发表时间：
2012-09-01
影响因子：
4.2
通讯作者：
Pollock, David M.
中科院分区：
文献类型：
--
作者：
Kittikulsuth, Wararat;Pollock, Jennifer S.;Pollock, David M.
王晓东，王晓东，王晓东，等。盐剥夺对肾髓质内皮素B受体功能的影响。[J] .中国医学工程学报，2016,31(1):559 - 566。2012年6月6日首次发表；doi: 10.1152 / ajprenal.00213.2012。-我们最近证明，慢性输注外源性ANG II，诱导血压升高，减弱大鼠肾髓内皮素B （ETB）受体功能。此外，这与肾内髓质中ETB受体表达的减少有关。本研究的目的是研究内源性ANG II（低盐饮食）生理增加对肾ET系统（包括ETB受体功能）的影响。我们假设内源性ANG II在低盐摄入时降低了肾髓ETB受体的功能。将大鼠置于低盐饮食（0.01-0.02% NaCl）中2周，以增加内源性ANG II。在正常盐饮食的大鼠中，ETB受体激动剂sarafotoxin 6c （S6c）刺激肾髓质ETB受体导致水（比基线增加3.6 +/- 0.4，比S6c输注后的10.5 +/- 1.3 μ l/min增加，P < 0.05）和钠排泄（0.38 +/- 0.06，比1.23 +/- 0.17 μ mol/min增加，P < 0.05）。低盐饮食降低了急性髓内输注S6c时etb依赖性利尿（4.5 +/- 0.5 vs. 6.1 +/- 0.9 μ mol/min）和钠尿（0.40 +/- 0.11 vs. 0.46 +/- 0.12 μ mol/min）。坎地沙坦慢性治疗可恢复肾髓ETB受体功能；尿流量分别为7.1 +/- 0.9 vs. 15.9 +/- 1.7 mu l/min (P < 0.05)，钠排泄量分别为0.4 +/- 0.1 vs. 1.1 +/- 0.1 mu mol/min （P < 0.05）。受体结合试验确定，与正常盐饮食的大鼠相比，无钠饮食导致肾内髓中ETB受体结合水平相似。坎地沙坦降低肾髓内ETB受体结合（1414 +/- 95 vs 862 +/- 50 fmol/mg; P < 0.05）。我们得出结论，内源性ANG II减弱了盐剥夺期间肾髓ETB受体的功能，从而独立于受体的表达来保存钠。
Kittikulsuth W, Pollock JS, Pollock DM. Loss of renal medullary endothelin B receptor function during salt deprivation is regulated by angiotensin II. Am J Physiol Renal Physiol 303: F659-F666, 2012. First published June 6, 2012; doi: 10.1152/ajprenal.00213.2012.-We have recently demonstrated that chronic infusion of exogenous ANG II, which induces blood pressure elevation, attenuates renal medullary endothelin B (ETB) receptor function in rats. Moreover, this was associated with a reduction of ETB receptor expression in the renal inner medulla. The aim of this present work was to investigate the effect of a physiological increase in endogenous ANG II (low-salt diet) on the renal ET system, including ETB receptor function. We hypothesized that endogenous ANG II reduces renal medullary ETB receptor function during low-salt intake. Rats were placed on a low-salt diet (0.01-0.02% NaCl) for 2 wk to allow an increase in endogenous ANG II. In rats on normal-salt chow, the stimulation of renal medullary ETB receptor by ETB receptor agonist sarafotoxin 6c (S6c) causes an increase in water (3.6 +/- 0.4 from baseline vs. 10.5 +/- 1.3 mu l/min following S6c infusion; P < 0.05) and sodium excretion (0.38 +/- 0.06 vs. 1.23 +/- 0.17 mu mol/min; P < 0.05). The low-salt diet reduced the ETB-dependent diuresis (4.5 +/- 0.5 vs. 6.1 +/- 0.9 mu l/min) and natriuresis (0.40 +/- 0.11 vs. 0.46 +/- 0.12 mu mol/min) in response to acute intramedullary infusion of S6c. Chronic treatment with candesartan restored renal medullary ETB receptor function; urine flow was 7.1 +/- 0.9 vs. 15.9 +/- 1.7 mu l/min (P < 0.05), and sodium excretion was 0.4 +/- 0.1 vs. 1.1 +/- 0.1 mu mol/min (P < 0.05) before and after intramedullary S6c infusion, respectively. Receptor binding assays determined that the sodium-depleted diet resulted in a similar level of ETB receptor binding in renal inner medulla compared with rats on a normal-salt diet. Candesartan reduced renal inner medullary ETB receptor binding (1,414 +/- 95 vs. 862 +/- 50 fmol/mg; P < 0.05). We conclude that endogenous ANG II attenuates renal medullary ETB receptor function to conserve sodium during salt deprivation independently of receptor expression.