Section of Experimental Medicine, Department of Medicine, Georgia Health Sciences University, Augusta, GA 30912, USA.
Am J Physiol Renal Physiol. 2012 Sep;303(5):F659-66. doi: 10.1152/ajprenal.00213.2012. Epub 2012 Jun 6.
We have recently demonstrated that chronic infusion of exogenous ANG II, which induces blood pressure elevation, attenuates renal medullary endothelin B (ET(B)) receptor function in rats. Moreover, this was associated with a reduction of ET(B) 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 ET(B) receptor function. We hypothesized that endogenous ANG II reduces renal medullary ET(B) 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 ET(B) receptor by ET(B) receptor agonist sarafotoxin 6c (S6c) causes an increase in water (3.6 ± 0.4 from baseline vs. 10.5 ± 1.3 μl/min following S6c infusion; P < 0.05) and sodium excretion (0.38 ± 0.06 vs. 1.23 ± 0.17 μmol/min; P < 0.05). The low-salt diet reduced the ET(B)-dependent diuresis (4.5 ± 0.5 vs. 6.1 ± 0.9 μl/min) and natriuresis (0.40 ± 0.11 vs. 0.46 ± 0.12 μmol/min) in response to acute intramedullary infusion of S6c. Chronic treatment with candesartan restored renal medullary ET(B) receptor function; urine flow was 7.1 ± 0.9 vs. 15.9 ± 1.7 μl/min (P < 0.05), and sodium excretion was 0.4 ± 0.1 vs. 1.1 ± 0.1 μmol/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 ET(B) receptor binding in renal inner medulla compared with rats on a normal-salt diet. Candesartan reduced renal inner medullary ET(B) receptor binding (1,414 ± 95 vs. 862 ± 50 fmol/mg; P < 0.05). We conclude that endogenous ANG II attenuates renal medullary ET(B) receptor function to conserve sodium during salt deprivation independently of receptor expression.
我们最近的研究表明，外源性血管紧张素 II 的慢性输注会引起血压升高，从而减弱大鼠肾脏髓质内皮素 B（ETB）受体的功能。此外，这与肾脏内髓质 ETB 受体表达的减少有关。本研究旨在探讨内源性血管紧张素 II 的生理性增加（低盐饮食）对肾脏 ET 系统的影响，包括 ETB 受体功能。我们假设内源性血管紧张素 II 在低盐摄入时会降低肾脏髓质 ETB 受体的功能。将大鼠置于低盐饮食（0.01-0.02% NaCl）2 周以增加内源性血管紧张素 II。在正常盐饮食的大鼠中，ETB 受体激动剂 Sarafotoxin 6c（S6c）刺激肾脏髓质 ETB 受体可引起水（基础值增加 3.6 ± 0.4 至 S6c 输注后增加 10.5 ± 1.3 μl/min；P < 0.05）和钠排泄（基础值增加 0.38 ± 0.06 至 S6c 输注后增加 1.23 ± 0.17 μmol/min；P < 0.05）。低盐饮食降低了急性向髓内输注 S6c 时 ETB 依赖性利尿（基础值增加 4.5 ± 0.5 至增加 6.1 ± 0.9 μl/min）和利钠作用（基础值增加 0.40 ± 0.11 至增加 0.46 ± 0.12 μmol/min）。坎地沙坦的慢性治疗恢复了肾脏髓质 ETB 受体的功能；向髓内输注 S6c 前后的尿量分别为 7.1 ± 0.9 比 15.9 ± 1.7 μl/min（P < 0.05），钠排泄量分别为 0.4 ± 0.1 比 1.1 ± 0.1 μmol/min（P < 0.05）。受体结合测定表明，与正常盐饮食的大鼠相比，低盐饮食导致肾脏内髓质 ETB 受体的结合水平相似。坎地沙坦降低了肾脏内髓质 ETB 受体的结合（1,414 ± 95 比 862 ± 50 fmol/mg；P < 0.05）。我们的结论是，内源性血管紧张素 II 通过独立于受体表达的方式在盐剥夺期间减弱肾脏髓质 ETB 受体的功能以保存钠。
