The urinary concentrating defect in the Gunn strain of rat. Role of bilirubin.
The role of high serum and tissue levels of unconjegated bilirubin in the pathogenesis of the impaired urinary concentrating ability was investigated in homozygous (jj) Gunn rats with the congenital absence of hepatic glucuronyl transferase. Continuous phototherapy with blue fluorescent lights at a wave length of 460 nm or oral cholestyramine feeding or both reduced serum levels of unconjugated hilirubin to levels consistently below 3.0 mg/100 ml for several weeks in both weanling and adult jj Gunn rats. The renal concentrating defect was already present in weanling jj Gunn rats by 21 days of age. In treated weanling jj animals, maximum concentrating ability and the concentration of urea and nonurea solutes in the papilla and medulla, determined after 24 h of fluid deprivation, were normal when compared to unaffected heterozygous (Jj) littermates. Solute-free water reabsorption which is reduced in jaundiced jj Gunn rats was restored to normal in treated weanling jj rats. The tissue concentration of unconjugated bilirubin was reduced throughout the papilla and inner and outer medulla in the treated jj rats in comparison with untreated jj littermates. The defect in urinary concentrating ability was only partially reversible and sometimes irreversible in adult jj rats, probably because of permanent renal parenchymal damage occurring secondary to massive crystalline deposits in the papilla and medulla. It is concluded that unconjugated bilirubin is directly involved in the pathogenesis of the concentrating defect in jaundiced jj Gunn rats.
D000818:Animals; D001663:Bilirubin / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000627:therapeutic use; D005260:Female; D006720:Homozygote; D006933:Hyperbilirubinemia, Hereditary / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy; D007444:Inulin / Q000097:blood / Q000652:urine; D007671:Kidney Concentrating Ability; D007672:Kidney Cortex / Q000032:analysis; D007679:Kidney Medulla / Q000032:analysis; D008297:Male; D009994:Osmolar Concentration; D010789:Phototherapy; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000032:analysis; D014508:Urea / Q000032:analysis; D014667:Vasopressins / Q000494:pharmacology
D014667:Vasopressins; D002792:Cholestyramine Resin; D014508:Urea; D007444:Inulin; D012964:Sodium; D001663:Bilirubin