Weinman E J, Knight T F, McKenzie R, Eknoyan G
Kidney Int. 1976 Oct;10(4):295-300. doi: 10.1038/ki.1976.112.
The tubular transport of urate and sodium was examined by clearance, free-flow micropuncture, intratubular microinjection and precession techniques in control rats and in rats receiving a new uricosuric diuretic, indanyloxyacetic acid (MK-196). The i.v. infusion of MK-196 (50 mg/kg of body wt/hr) resulted in significant increases in the fractional excretion of sodium (FENa) from 0.98 +/- 0.01 to 11.86 +/- 2.88% (P less than 0.001) and in FEurate from 14.1 +/- 1.03 to 56.0 +/- 2.86% (P less than 0.001). End-proximal tubular fluid to plasma inulin (TF/Pinulin) ratios were 2.43 +/- 0.15 and 2.51 +/- 0.10 in control and drug-treated animals, respectively (P = NS). Total urinary urate recovery after MK-196 administration was higher following microinjections of [2-14C] urate into early proximal tubule sites: 70.5 +/- 2.7% in controls vs. 84.9 +/- 0.9 (P less than 0.001), and after microinjections into late proximal tubule sites: 82.8 +/- 2.9% vs. 91.3 +/- 1.9 (P less than 0.05). Urinary precession of urate from inulin was demonstrable following placement of isotopes of these compounds on the surface of the kidney in controls, but was abolished by MK-196. This agent, therefore, inhibits the reabsorption and secretion of urate in the proximal convoluted tubule, the net effect being a marked increase in urinary urate excretion. By contrast, its inhibitory effect on sodium reabsorption is exerted at a site or sites distal to the accessible portion of the proximal tubule. The demonstration of reduced urate reabsorption and normal sodium reabsorption in the proximal tubule suggests that the reabsorption of these constituents of the glomerular filtrate is not intimately linked at this nephron site.
通过清除率、自由流动微穿刺、肾小管内微注射和追踪技术，对正常大鼠以及接受新型促尿酸尿性利尿剂茚满氧基乙酸（MK - 196）的大鼠的尿酸盐和钠的肾小管转运进行了研究。静脉输注MK - 196（50毫克/千克体重/小时）导致钠的分数排泄（FENa）从0.98±0.01显著增加至11.86±2.88%（P＜0.001），尿酸盐的分数排泄（FEurate）从14.1±1.03增加至56.0±2.86%（P＜0.001）。在正常动物和药物处理动物中，近端肾小管液与血浆菊粉（TF/Pinulin）的比率分别为2.43±0.15和2.51±0.10（P =无显著差异）。在早期近端肾小管部位微注射[2 - 14C]尿酸盐后，MK - 196给药后的总尿尿酸盐回收率更高：正常组为70.5±2.7%，而药物处理组为84.9±0.9（P＜0.001）；在晚期近端肾小管部位微注射后，正常组为82.8±2.9%，药物处理组为91.3±1.9（P＜0.05）。在正常大鼠中，将这些化合物的同位素置于肾表面后，可证明尿酸盐相对于菊粉的尿追踪现象，但MK - 196可消除该现象。因此，该药物抑制近端曲管中尿酸盐的重吸收和分泌，其净效应是尿尿酸盐排泄显著增加。相比之下，其对钠重吸收的抑制作用发生在近端小管可及部分的远端一个或多个部位。近端小管中尿酸盐重吸收减少而钠重吸收正常，这表明肾小球滤过液中这些成分的重吸收在该肾单位部位并非紧密相关。
