Role of endothelin B receptor in the pathogenesis of ischemic acute renal failure.
This study evaluated the role of endothelin B (ET ) receptor-mediated action in the development and maintenance of ischemic acute renal failure (ARF), using the spotting-lethal ( ) rat that carries a naturally occurring deletion in the ET receptor gene. Because homozygous ( ) rats die shortly after birth due to congenital distal intestinal aganglionosis, genetic rescue of rats from the developmental defect using a dopamine-beta-hydroxylase (DbetaH)-ET transgene was performed to produce ET -deficient adult rats. Rescued homozygous (DbetaH-ET ) and wild-type (DbetaH-ET +/+) rats were subjected to ischemic ARF by clamping the renal pedicle for 45 min followed by reperfusion. At 24 h after the reperfusion, renal glomerular dysfunction and histologic damage, such as proteinaceous casts in tubuli, were markedly and observed equally in homozygous and wild-type groups, and these renal injuries gradually recovered. However, when the ischemia/reperfusion-induced renal injury was examined 7 days after the reperfusion, the recovery in homozygous ARF rats was obviously delayed compared with the wild-type animals. Two of the eight homozygous ARF rats died within 3 days after the reperfusion. Increment of renal endothelin-1 content after the ischemia/reperfusion was more marked in homozygous than in wild-type rats. Thus, ET receptor-mediated actions do not play an important role in the development of ischemic ARF but may be involved in the recovery process from ischemia/reperfusion-induced renal injury.
D058186:Acute Kidney Injury / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D030801:Animals, Genetically Modified; D019332:Endothelin-1 / Q000378:metabolism; D007511:Ischemia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D051381:Rats; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D019332:Endothelin-1; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin