Role of endothelin B receptor in the pathogenesis of ischemic acute renal failure

• Published in: Journal of cardiovascular pharmacology Vol. 40; no. 4; p. 586
• Main Authors: Nishida, Masahiro, Ieshima, Miyuki, Konishi, Fumiko, Yamashita, Junji, Takaoka, Masanori, Matsumura, Yasuo
• Format: Journal Article
• Language: English
• Published: United States 01.10.2002
• Subjects: Acute Kidney Injury - genetics; Acute Kidney Injury - pathology; Acute Kidney Injury - physiopathology; Animals; Animals, Genetically Modified; Endothelin-1 - metabolism; Ischemia - genetics; Ischemia - pathology; Ischemia - physiopathology; Kidney - blood supply; Kidney - pathology; Rats; Receptor, Endothelin B; Receptors, Endothelin - deficiency; Receptors, Endothelin - genetics; Receptors, Endothelin - physiology
• ISSN: 0160-2446
• DOI: 10.1097/00005344-200210000-00012

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.