Role of nitric oxide and prostaglandin E2 in acute renal hypoperfusion
Role of nitric oxide and prostaglandin E2 in acute renal hypoperfusion
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一氧化氮和前列腺素 E2 在急性肾低灌注中的作用
作者：
H. Tokuyama;K. Hayashi;H. Matsuda;E. Kubota;M. Honda;K. Okubo;I. Takamatsu;Y. Ozawa;T. Saruta
总结：虽然急性肾缺血改变了各种旁分泌的产生，但很少有研究探讨肾内血管活性物质的作用。在本研究中，我们研究了肾内一氧化氮和洋地黄素在调节急性肾灌注不足引起的肾功能改变中的作用。在左肾动脉90%夹闭60 min后，释放夹子，并在麻醉犬的夹闭和未夹闭肾脏中评价肾脏血流动力学和钠排泄。 采用肾微透析技术检测肾组织中硝酸盐/亚硝酸盐（NOx）和前列腺素E2（PGE 2）含量的变化。释放夹引起肾血浆流量和肾小球滤过率的逐渐恢复，以及夹闭肾脏中钠排泄分数（FENa）的持续增加。肾皮质和髓质组织中的NOx含量分别从8.2 ± 1.1 μ mol/L和10.1 ± 0.9 μ mol/L降至2.5 ± 0.3μmol/L（P <0.01），但开放后逐渐升高。 硝基-L-精氨酸甲酯治疗仅轻度损害肾血浆流量（RPF;第4小时）和肾小球滤过率（GFR;开放后3小时和4小时）的恢复，而不影响FENa。肾组织PGE 2水平在缺血发作时显著升高（髓质从149 ± 19升至378 ± 39 pg/mL，P <0.01;皮质从107 ± 13升至302 ± 34 pg/mL，P <0.01）。 此外，用非特异性环加氧酶（考克斯）抑制剂磺比林和考克斯-2特异性抑制剂NS 398预处理，以类似方式显著抑制急性肾动脉夹闭诱导的FENa增加。总之，在急性肾低灌注时，一氧化氮（NO）在肾血流动力学的恢复中起着允许的作用。相比之下，在夹闭和非夹闭的肾脏中，肾脏PGE 2的持续增加表明考克斯-2介导的PGE 2对急性肾灌注不足引起的钠重吸收失败有重要作用。
SUMMARY: Although acute renal ischaemia alters the production of various paracrines, there has been little investigation examining the role of intrarenal vasoactive substances. In the present study, we investigated the role of intrarenal nitric oxide and prostaglandins in modulating the acute renal hypoperfusion‐induced alterations in renal function. After a 90% clipping of the left renal artery for 60 min, the clip was released, and the renal haemodynamics and sodium excretion were evaluated in both clipped and non‐clipped kidneys of anaesthetized dogs. Furthermore, the changes in renal contents of nitrate/nitrite (NOx) and prostaglandin E2 (PGE2) were assessed by using the renal microdialysis technique. The release of the clipping elicited a gradual recovery of renal plasma flow and glomerular filtration rate, and a sustained increase in fractional sodium excretion (FENa) in the clipped kidney. Renal interstitial NOx was reduced in both the cortex (from 8.2 ± 1.1 to 2.5 ± 0.3 µmol/L, P < 0.01) and medulla (from 10.1 ± 0.9 to 3.1 ± 0.2 µmol/L, P < 0.01), but the levels gradually elevated after declamping. The treatment with nitro‐l‐arginine methylester only modestly impaired the recovery of renal plasma flow (RPF; at hour 4) and glomerular filtration rate (GFR; at hours 3 and 4 after declamping), without affecting FENa. Conversely, the renal PGE2 levels increased prominently upon the onset of ischaemia (medulla, from 149 ± 19 to 378 ± 39 pg/mL, P < 0.01; cortex, from 107 ± 13 to 302 ± 34 pg/mL, P < 0.01). Furthermore, the pretreatment with a non‐specific cyclo‐oxygenase (COX) inhibitor, sulpyrine, and a COX‐2‐specific inhibitor, NS398, prominently inhibited the increases in FENa induced by the acute renal arterial clipping in a similar manner. In conclusion, in acute renal hypoperfusion, nitric oxide (NO) plays a permissive role in the recovery of the renal haemodynamics. In contrast, sustained increases in renal PGE2 in both clipped and non‐clipped kidneys indicate that the COX‐2‐mediated PGE2 contributes importantly to the failure of the sodium reabsorption in response to acute renal hypoperfusion.
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DOI：
10.1681/asn.v16875
发表时间：
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影响因子：
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DOI：
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发表时间：
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期刊：
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影响因子：
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DOI：
10.1152/ajprenal.1992.262.6.f943
发表时间：
1992
期刊：
The American journal of physiology
影响因子：
--
作者：
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通讯作者：
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