Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
PLoS One. 2011;6(10):e26063. doi: 10.1371/journal.pone.0026063. Epub 2011 Oct 7.
The renal medullary endothelin (ET-1) system plays an important role in the control of sodium excretion and arterial pressure (AP) through the activation of renal medullary ET-B receptors. We have previously shown that blockade of endothelin type B receptors (ET-B) leads to salt-sensitive hypertension through mechanisms that are not fully understood. One possible mechanism is through a reduction in renal medullary production of 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE, a metabolite of arachidonic acid, has natriuretic properties similar to ET-B activation. While these findings suggest a possible interaction between ET-B receptor activation and 20-HETE production, it is unknown whether blockade of medullary ET-B receptors in rats maintained on a high sodium intake leads to reductions in 20-HETE production.
METHODOLOGY/PRINCIPAL FINDINGS: The effect of increasing sodium intake from low (NS = .8%) to high (HS = 8%) on renal medullary production of 20-HETE in the presence and absence of renal medullary ET-B receptor antagonism was examined. Renal medullary blockade of ET-B receptors resulted in salt sensitive hypertension. In control rats, blood pressure rose from 112.8±2.4 mmHg (NS) to 120.7±9.3 mmHg (HS). In contrast, when treated with an ET-B receptor blocker, blood pressure was significantly elevated from 123.7±3.2 (NS) to 164.2±7.1 (HS). Furthermore, increasing sodium intake was associated with elevated medullary 20-HETE (5.6±.8 in NS vs. 14.3±3.7 pg/mg in HS), an effect that was completely abolished by renal medullary ET-B receptor blockade (4.9±.8 for NS and 4.5±.6 pg/mg for HS). Finally, the hypertensive response to intramedullary ET-B receptor blockade was blunted in rats pretreated with a specific 20-HETE synthesis inhibitor.
These data suggest that increases in renal medullary production of 20-HETE associated with elevating salt intake may be, in part, due to ET-B receptor activation within the renal medulla.
肾髓质内皮素（ET-1）系统通过激活肾髓质 ET-B 受体在控制钠排泄和动脉压（AP）方面发挥重要作用。我们之前的研究表明，内皮素 B 受体（ET-B）阻断会导致盐敏感型高血压，其机制尚不完全清楚。一种可能的机制是通过减少肾髓质 20-羟二十碳四烯酸（20-HETE）的产生。20-HETE 是花生四烯酸的代谢物，具有类似于 ET-B 激活的利尿特性。虽然这些发现表明 ET-B 受体激活和 20-HETE 产生之间可能存在相互作用，但尚不清楚在高盐摄入的大鼠中阻断肾髓质 ET-B 受体是否会导致 20-HETE 产生减少。
方法/主要发现：研究了在存在和不存在肾髓质 ET-B 受体拮抗的情况下，从低钠（NS = 0.8%）增加到高钠（HS = 8%）对肾髓质 20-HETE 产生的影响。肾髓质 ET-B 受体阻断导致盐敏感型高血压。在对照大鼠中，血压从 112.8±2.4 mmHg（NS）升高至 120.7±9.3 mmHg（HS）。相比之下，当用 ET-B 受体阻滞剂治疗时，血压从 123.7±3.2（NS）显著升高至 164.2±7.1（HS）。此外，增加钠摄入量与髓质 20-HETE 升高相关（5.6±0.8 在 NS 时与 14.3±3.7 pg/mg 在 HS 时），该作用完全被肾髓质 ET-B 受体阻断所消除（4.9±0.8 在 NS 时和 4.5±0.6 pg/mg 在 HS 时）。最后，在预先用特异性 20-HETE 合成抑制剂处理的大鼠中，内髓 ET-B 受体阻断的高血压反应减弱。
这些数据表明，与盐摄入量增加相关的肾髓质 20-HETE 产生增加部分可能是由于肾髓质内 ET-B 受体的激活。
