Subject(s)
Anticoagulants/metabolism , Aryl Hydrocarbon Hydroxylases/genetics , Aryl Hydrocarbon Hydroxylases/metabolism , Genetic Variation , Warfarin/metabolism , Aged , Base Sequence , Cytochrome P-450 CYP2C9 , DNA/genetics , DNA Primers/genetics , Female , Genotype , Humans , Male , Pedigree , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthABSTRACT
We investigated the role of endothelin ET(B) receptor in the remnant kidney model of chronic renal failure, by using the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the endothelin ET(B) receptor gene. After 5/6 nephrectomy, systolic blood pressure and renal functional parameters were measured for 12 weeks. At the end of the experimental period, arterial blood sample, remnant kidney, heart and aorta were collected and used for biochemical measurements and histopathological studies. The ET(B)-deficient sl/sl rats exhibited earlier and higher increases in systolic blood pressure, urinary protein excretion, blood urea nitrogen and plasma creatinine concentration, compared with cases in wild-type rats. Histopathologic examination of the kidney revealed glomerular and tubular lesions, alterations of which were more severe in sl/sl than in wild-type rats. While aortic endothelin-1 contents were increased similarly in both groups, the level of renal endothelin-1 content was significantly elevated in sl/sl rats, but not in the wild-type rats. These results suggest that enhanced endothelin-1 production is at least partly responsible for the increased susceptibility to partial ablation-induced chronic renal failure in ET(B) receptor-deficient rats and that ET(B) receptor-mediated actions are protective against vascular and renal injuries in this disease.
Subject(s)
Catheter Ablation/methods , Kidney Failure, Chronic/metabolism , Receptor, Endothelin B/physiology , Animals , Kidney Failure, Chronic/genetics , Male , Rats , Rats, Mutant Strains , Rats, Sprague-Dawley , Receptor, Endothelin B/deficiency , Receptor, Endothelin B/geneticsABSTRACT
The role of endothelin-B (ETB) receptor in partial ablation-induced chronic renal failure was evaluated using the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the ETB receptor gene. After 5/6 nephrectomy in ETB-deficient homozygous and wild-type (+/+) rats, we measured the systolic blood pressure and renal functional parameters for 12 weeks. At the end of the experimental period, we collected an arterial blood sample and excised the remnant kidney, heart and aorta for biochemical measurements and histopathological studies. The ETBdeficient homozygous rats exhibited earlier and higher increases in systolic blood pressure, urinary protein excretion, blood urea nitrogen and plasma creatinine concentration, compared with cases in wild-type rats. Histopathologic examination of the kidney revealed glomerular and tubular lesions, alterations of which were more severe in homozygous than in wild-type rats. There was a significant increase in the renal endothelin-1 content in homozygous rats, but not in the wild-type rats. However, the aortic endothelin-1 contents were increased similarly in both groups. These results suggest that enhanced endothelin-1 production is at least partly responsible for the increased susceptibility to partial ablationinduced chronic renal failure in ETB receptor-deficient rats and that ETB receptor-mediated actions are protective against vascular and renal injuries in this disease.
