CYSTEINYL LEUKOTRIENE ACTIONS ON THE MICROCIRCULATION OF THE NORMAL AND SPLIT HYDRONEPHROTIC RAT-KIDNEY

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-mu-g 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.