Inhibition of renal outer medullary 20-HETE production produces hypertension in Lewis rats
Inhibition of renal outer medullary 20-HETE production produces hypertension in Lewis rats
复制标题
DOI：
10.1161/01.hyp.29.1.315
复制
发表时间：
1997-01-01
期刊：
影响因子：
8.3
通讯作者：
Roman, RJ
中科院分区：
文献类型：
--
作者：
Stec, DE;Mattson, DL;Roman, RJ
最近的研究表明，20-羟基二十碳四烯酸（20-HETE）在肾脏的外髓质生产的不足，可能会导致异常的肾脏处理钠和高血压的发展达尔盐敏感大鼠。为了确定外髓质中20-HETE产生的减少是否足以诱导高血压，将花生四烯酸通过P450酶的肾代谢的抑制剂17-十八碳烯酸（17-ODYA）直接长期输注到喂食高盐饮食的单侧肾切除的刘易斯大鼠的左肾外髓质中。肾髓质间质输注17-ODYA（400 pmol/min）使输注肾脏外髓质中20-HETE的形成减少了70%，与大鼠单侧肾切除后收集的右肾中的值相比，但对肾皮质中20-HETE的产生没有影响。5天后，输注17-ODYA的大鼠的平均动脉压从115 +/-2上升到142 +/-2 mm Hg（n = 6），而仅输注载体的大鼠的平均动脉压没有显著改变（116 +/-1对117 +/-2 mm Hg，n = 6）。这些结果表明，肾脏外髓质中P450酶抑制花生四烯酸的肾脏代谢足以诱导高盐饮食刘易斯大鼠发生高血压，并支持花生四烯酸的P450代谢物在肾功能调节和动脉压的长期控制中起重要作用的观点。
Recent studies have indicated that a deficiency in the production of 20-hydroxyeicosatetraenoic acid (20-HETE) in the outer medulla of the kidney may contribute to the abnormalities in the renal handling of sodium and the development of hypertension in Dahl salt-sensitive rats. To determine whether a reduction in 20-HETE production in the outer medulla is sufficient to induce hypertension, an inhibitor of the renal metabolism of arachidonic acid by P450 enzymes, 17-octadecenoic acid (17-ODYA), was chronically infused directly into the outer medulla of the left kidney of uninephrectomized Lewis rats fed a high salt diet. Renal medullary interstitial infusion of 17-ODYA (400 pmol/min) reduced the formation of 20-HETE in the outer medulla of the infused kidney by 70% compared with values seen in the right kidney collected when the rat was uninephrectomized, but it had no effect on the production of 20-HETE in the renal cortex. After 5 days, mean arterial pressure rose from 115 +/- 2 to 142 +/- 2 mm Hg (n = 6) in the rats infused with 17-ODYA, while mean arterial pressure was not significantly altered in the rats infused with vehicle alone (116 +/- 1 versus 117 +/- 2 mm Hg, n = 6). These results suggest that inhibition of the renal metabolism of arachidonic acid by P450 enzymes in the outer medulla of the kidney is sufficient to induce the development of hypertension in Lewis rats fed a high salt diet and support the view that P450 metabolites of arachidonic acid play an important role in the regulation of renal function and the long-term control of arterial pressure.