Upregulation of Endothelin A Receptor Sites in the Rabbit Diabetic Kidney: Potential Relevance to the Early Pathogenesis of Diabetic Nephropathy

Publisher Website
Google Scholar
Abstract
Background/Aim: Nephropathy is an important complication of diabetes mellitus (DM). The plasma endothelin 1 (ET-1) levels are increased in DM, and ET-1 may cause deleterious effects on renal function. We, therefore, investigated whether changes in ET receptors occur in the DM rabbit kidney. Methods: Nine adult New Zealand White rabbits were injected with alloxan, of which 6 became diabetic; the other 3 acted as alloxan-treated controls. Six age-matched healthy rabbits served as controls. At 6 months, following cervical dislocation, the kidneys were removed, and sections (cortex and medulla) were incubated with ETA and ETB radioligands to produce low- and high-resolution autoradiographs. Immunohistochemical localization of ET-1 immunoreactivity was also performed. Results: There was greater ETA and ETB receptor binding in the control (ETA p = 0.0003; ETB p < 0.0001) and DM (ETA p = 0.001; ETB p < 0.0001) rabbits in the medulla as compared with the cortex. DM kidneys showed a significant increase in ETA, but not ETB, binding in the cortex (p < 0.0001) and in the medulla (p < 0.0001). High-resolution autoradiographs revealed striking [125I]-ET-1 receptor binding predominantly to the glomeruli. Immunohistochemistry revealed dense ET-1 immunoreactivity associated with the renal tubules, but the glomeruli exhibited no staining. Alloxan-treated controls had similar results to age-matched controls. Conclusion: There are regional differences in both ETA and ETB binding in control and DM kidneys. ETA receptor binding sites are increased in the DM kidney (cortex and medulla). ET-1 may act in a paracrine fashion on the glomeruli. These changes may contribute to the pathogenesis of diabetic nephropathy.

This publication has 2 references indexed in Scilit: