Changes in medullary glycosaminoglycan histochemistry and microvascular filling during the development of 2-bromoethanamine hydrobromide-induced renal papillary necrosis.
A single dose of 2-bromoethanamine (BEA) hydrobromide induced an apex limited renal papillary necrosis (RPN) at low doses (50 mg/kg, ip and sc, or 100 mg/kg, po), and the total ablation of the medulla at high doses (greater than 150 mg/kg, ip and sc, or 1000 mg/kg, po) in both male and female Wistar rats. BEA (at levels of 50, 100, and 150 mg/kg ip to male rats) caused transient hydropic changes. By 12 to 24 hr the anatomical elements of the medulla were necrosed, and active regeneration and reepithelialization of the viable areas was apparent. The only cortical changes up to 120 hr were dilatation of the nephron and the Bowman's spaces. The medullary glycosaminoglycan matrix (assessed by histochemical staining with colloidal iron) gave an intense granular appearance 2 hr after BEA, which was more marked and diffuse in the apex of the medulla from 8 to 12 hr. The staining was lost from those areas where early necrotic changes had occurred by 12 to 24 hr, and there was no subsequent staining of matrix material up to 120 hr. Vascular filling with colloidal carbon particles suggested an early shift of blood flow to the outer medulla at 2 to 4 hr, followed by the sustained filling of the microvasculature of the medulla well into the period when frank necrotic change was apparent. These data suggest that changes in the medullary matrix might play a previously unrecognized role in the development of 2-bromoethanamine hydrobromide-induced renal papillary necrosis, and these changes may give rise to loss of the material that supports the medullary capillaries.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000633:toxicity*; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism*; D006651:Histocytochemistry; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008297:Male; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects
D005021:Ethylamines; D006025:Glycosaminoglycans; C004504:2-bromoethylamine