Role of 20-hydroxyeicosatetraenoic acid in mediating hypertension in response to chronic renal medullary endothelin type B receptor blockade.
Role of 20-hydroxyeicosatetraenoic acid in mediating hypertension in response to chronic renal medullary endothelin type B receptor blockade.
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DOI：
10.1371/journal.pone.0026063
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Granger JP
中科院分区：
文献类型：
--
作者：
Speed JS;George EM;Arany M;Cockrell K;Granger JP
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)中发挥重要作用。我们之前已经证明，阻断内皮素B型受体(ET-B)可通过尚未完全了解的机制导致盐敏感型高血压。一个可能的机制是通过减少肾髓质产生20-羟基二十碳四烯酸(20-HETE)。20-HETE是花生四烯酸的代谢物，具有类似于ET-B激活的利钠特性。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，但在维持高钠摄入量的大鼠中，阻断延髓ET-B受体是否会导致20-HETE产生减少尚不清楚。本文观察了在存在和不存在肾髓质ET-B受体拮抗剂的情况下，钠摄入量从低钠(NS = .8%)增加到高钠(HS = 8%)对20-HETE产生的影响。肾延髓阻断ET-B受体导致盐敏感型高血压。对照组大鼠血压从112.8±2.4毫米汞柱(NS)升至120.7±9.3毫米汞柱(HS)。相反，当接受ET-B受体阻滞剂治疗时，血压显著升高，从123.7±3.2NS升至164.2±7.1HS。此外，钠摄入量的增加与延髓20-HETE的升高有关(NS为5.6±0.8，HS为14.3±3.7pg/mg)，这种作用可被肾延髓ET-B受体阻滞剂完全消除(NS为4.9±0.8，HS为4.5±.6pg/mg)。最后，用一种特定的20-HETE合成抑制剂处理的大鼠，对延髓内ET-B受体阻断的高血压反应是钝化的。这些数据表明，随着盐摄入量的增加，肾髓质产生的20-HETE增加，部分原因可能是肾髓质内ET-B受体的激活。
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. 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.
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影响因子：
13.6
作者：
Pavlov, Tengis S.;Chandi, Ahmed;Staruschenko, Alexander
通讯作者：
Staruschenko, Alexander
影响因子：
15.9
作者：
Ahn, D;Ge, YQ;Kohan, DE
通讯作者：
Kohan, DE
影响因子：
8.3
作者：
Stec, DE;Mattson, DL;Roman, RJ
通讯作者：
Roman, RJ
DOI：
10.1152/ajprenal.2001.281.1.f144
发表时间：
2001-07-01
影响因子：
4.2
作者：
Pollock, DM;Pollock, JS
通讯作者：
Pollock, JS
影响因子：
8.3
作者：
Williams, JM;Zhao, XY;Pollock, DM
通讯作者：
Pollock, DM