Gulbins E, Parekh N, Rauterberg E W, Schlottmann K, Steinhausen M
1st Institute of Physiology, University of Heidelberg, FRG.
Eur J Clin Invest. 1991 Apr;21(2):184-96. doi: 10.1111/j.1365-2362.1991.tb01808.x.
The effects of leukotriene D4 (LTD4) and leukotriene E4 (LTE4) on renal microcirculation were determined on normal and hydronephrotic female Wistar rats. In normal kidneys, the effects of LTD4 on total renal blood flow and glomerular filtration rate were measured by a flow meter and by inulin clearance. In the split hydronephrotic kidney, the LTD4- and LTE4-mediated vascular effects were localized by intravital microscopy. Intravenous infusion of low-dose LTD4 (1 x 10(-9) mol min-1 kg-1) over 15 min induced a strong decrease in renal blood flow (-43% and -70%) in the normal and the hydronephrotic kidney. After the infusion the glomerular filtration rate of the normal kidney was significantly reduced by 65% and the filtration fraction by 32%. The fall in filtration fraction is in accordance with the significant decrease in luminal diameters of the arcuate artery (-28%) and the proximal interlobular artery (-12%) in the hydronephrotic kidney under LTD4. The decrease in renal blood flow, glomerular filtration rate, filtration fraction and luminal diameters persisted in the normal as well as in the hydronephrotic kidney for more than 60 min beyond cessation of infusion. Local application of LTD4 (1 x 10(-10) mol l-1 up to 1 x 10(-7) mol l-1) and LTE4 (1 x 10(-10) mol l-1 up to 1 x 10(-8) mol l-1) induced a dose-dependent constriction of the arcuate artery and the proximal interlobular artery. The distal interlobular artery, the afferent and the efferent arteriole were not significantly affected by LTD4 or LTE4. The glomerular blood flow was dose-dependently reduced up to 48% under local LTD4 and 43% under LTE4. The LTD4/LTE4 antagonist FPL 55712 (1 x 10(-8) mol min-1 kg-1, iv) significantly attenuated the effects of LTD4 infusion and local LTE4 application in the hydronephrotic kidney. This is indicative of the presence of receptors for LTD4 and LTE4 in the larger preglomerular vessels of the rat kidney. The LTD4 effects on the normal kidney were attenuated by simultaneous infusion of dopamine (5 microgram min-1 kg-1) or plasma expansion, two principal methods in the treatment of acute renal failure. The results in the normal and hydronephrotic kidney demonstrate a preferential preglomerular vasoconstriction under LTD4 and LTE4 causing a marked decrease in renal and glomerular blood flow, glomerular filtration rate and filtration fraction.
在正常和肾积水的雌性Wistar大鼠身上测定了白三烯D4（LTD4）和白三烯E4（LTE4）对肾微循环的影响。在正常肾脏中，通过流量计和菊粉清除率测量LTD4对总肾血流量和肾小球滤过率的影响。在分离的肾积水肾脏中，通过活体显微镜观察LTD4和LTE4介导的血管效应的定位。静脉输注低剂量LTD4（1×10⁻⁹mol·min⁻¹·kg⁻¹）15分钟，可使正常和肾积水肾脏的肾血流量显著降低（分别降低43%和70%）。输注后，正常肾脏的肾小球滤过率显著降低65%，滤过分数降低32%。滤过分数的下降与LTD4作用下肾积水肾脏中弓形动脉（-28%）和小叶间动脉近端（-12%）管腔直径的显著减小一致。肾血流量、肾小球滤过率、滤过分数和管腔直径的降低在正常和肾积水肾脏中在输注停止后持续超过60分钟。局部应用LTD4（1×10⁻¹⁰mol·L⁻¹至1×10⁻⁷mol·L⁻¹）和LTE4（1×10⁻¹⁰mol·L⁻¹至1×10⁻⁸mol·L⁻¹）可引起弓形动脉和小叶间动脉近端剂量依赖性收缩。小叶间动脉远端、入球小动脉和出球小动脉不受LTD4或LTE4的显著影响。局部应用LTD4时肾小球血流量剂量依赖性降低达48%，应用LTE4时降低达43%。LTD4/LTE4拮抗剂FPL 55712（1×10⁻⁸mol·min⁻¹·kg⁻¹，静脉注射）可显著减弱LTD4输注和局部应用LTE4在肾积水肾脏中的作用。这表明大鼠肾脏较大的肾小球前血管中存在LTD4和LTE4受体。LTD4对正常肾脏的作用可通过同时输注多巴胺（5μg·min⁻¹·kg⁻¹）或扩容来减弱，这是治疗急性肾衰竭的两种主要方法。正常和肾积水肾脏的结果表明，在LTD4和LTE4作用下肾小球前血管优先收缩，导致肾血流量、肾小球血流量、肾小球滤过率和滤过分数显著降低。
