Nephron obstruction in nordihydroguaiaretic acid-induced renal cystic disease.
Studies were performed to characterize conditions in rat kidneys whose nephrons were made cystic by feeding 2% nordihydroguaiaretic acid (NDGA) to the animals. Using two micropipettes, we monitored intratubular hydrostatic pressures while perfusing single surface nephrons in NDGA-exposed (5 to 7 weeks) and normal rat kidneys. The introduction of 50 nl of Ringers solution labeled with 3H-inulin at a flow rate of 25 nl/min was associated with a significant mean (+/- SEM) increase (167 +/- 61%; P less than 0.02) in pressure in cystic but not in nondilated (-0.5 +/- 27.2%) or normal (31 +/- 23%) nephrons, respectively. The relative amount of 3H-inulin excreted in 40 min from cystic (4.0 +/- 2.0%) was less than that excreted from either nondilated (19 +/- 7%; P less than 0.05) or normal (105 +/- 26%; P less than 0.01) nephrons. Intralumenal pressures in nondilated but not other nephron groups correlated with urinary flow rates (r = 0.51; P less than 0.02). Single nephron filtration rates and tubular-fluid-to-plasma 3H-inulin rations in additional rats were similar among all groups of tubules. Concluding that these data reflected increased resistance to outflow from cystic nephrons, we examined these and additional NDGA-exposed (1 to 24 weeks) kidneys. 3H-thymidine radioautography demonstrated maximum collecting tubular cell hyperplasia (13% labeling) at 2 to 3 weeks of NDGA-exposure. Microscopy and microdissection demonstrated tiny mural polyps along outer medullary segments of collecting tubules. Thirteen tubules were traced to their outlets; polyps impinging on outflow lumens were found in all 13 instances. We conclude that partial nephron obstruction exists in NDGA-exposed kidneys and that obstruction is a likely contributor to cyst formation in this model.
D000818:Animals; D006138:Guaiac / Q000031:analogs & derivatives*; D006965:Hyperplasia / Q000139:chemically induced; D007444:Inulin / Q000378:metabolism / Q000494:pharmacology; D052177:Kidney Diseases, Cystic / Q000139:chemically induced* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007685:Kidney Tubules, Collecting / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D009399:Nephrons / Q000473:pathology* / Q000648:ultrastructure; D010477:Perfusion; D011127:Polyps / Q000139:chemically induced; D011312:Pressure; D051381:Rats; D013997:Time Factors
D006138:Guaiac; D007444:Inulin