Evans R G, Day K H, Roman R J, Hopp K H, Anderson W P
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Am J Hypertens. 1998 Jul;11(7):803-12. doi: 10.1016/s0895-7061(98)00045-4.
To characterize the role of cytochrome P450 metabolism of fatty acids in the renal response to increased renal perfusion pressure, we tested the effects of renal arterial infusion of 17-octadecynoic acid (17-ODYA, 450 nmol/min) on renal and systemic hemodynamic, and renal excretory responses to step-wise increases in renal perfusion pressure (RPP) in anesthetized rabbits, using an extracorporeal circuit for renal autoperfusion. Inhibition of cytochrome P450-dependent fatty acid metabolism was estimated by comparing the metabolism of arachidonic acid in microsomes prepared from the kidneys of control and 17-ODYA-treated animals. Step-wise increases in RPP decreased mean arterial pressure, which previous studies have indicated is attributable to the release of a depressor hormone from the renal medulla. Elevations in RPP also increased renal blood flow and glomerular filtration rate, and the absolute and fractional excretions of urine and sodium. Intrarenal infusion of 17-ODYA reduced the metabolism of arachidonic acid to 20-hydroxyeicosatetraenoic acid by 41%, but it did not significantly influence the responses to increased renal perfusion pressure. We conclude that either the responses elicited by increased renal perfusion pressure in anesthetized rabbits do not depend on cytochrome P450-dependent fatty acid metabolism, or that cytochrome P450 activity must be inhibited by more than was achieved in the present study (41%), before functional effects on the response to increased renal perfusion pressure are observed.
为了明确脂肪酸的细胞色素P450代谢在肾脏对肾灌注压升高反应中的作用，我们利用体外肾自身灌注回路，测试了肾动脉输注17 - 十八碳炔酸（17 - ODA，450 nmol/分钟）对麻醉兔的肾脏和全身血流动力学以及肾脏对肾灌注压（RPP）逐步升高的排泄反应的影响。通过比较对照动物和17 - ODA处理动物肾脏制备的微粒体中花生四烯酸的代谢情况，评估细胞色素P450依赖性脂肪酸代谢的抑制作用。RPP逐步升高会降低平均动脉压，先前的研究表明这归因于肾髓质释放的一种降压激素。RPP升高还会增加肾血流量和肾小球滤过率，以及尿液和钠的绝对排泄量和排泄分数。肾内输注17 - ODA使花生四烯酸向20 - 羟基二十碳四烯酸的代谢减少了41%，但它并未显著影响对肾灌注压升高的反应。我们得出结论，要么麻醉兔肾灌注压升高引发的反应不依赖于细胞色素P450依赖性脂肪酸代谢，要么在观察到对肾灌注压升高反应的功能影响之前，细胞色素P450活性必须受到比本研究中所达到的程度（41%）更大程度的抑制。
