Premium
ET A receptor dependent increases in glomerular permeability in experimentally induced diabetic rats
Author(s) -
Saleh Mohamed A.,
Pollock Jennifer S.,
Savin Virginia J.,
Pollock David M.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.971.3
Subject(s) - endocrinology , medicine , streptozotocin , chemistry , albuminuria , albumin , oncotic pressure , receptor , diabetes mellitus , saline , antagonist
A glomerular permeability defect occurs early in type 1 diabetes and precedes the onset of albuminuria and renal morphological changes. The aim of the current study was to test the hypothesis that the ET A receptor contributes to increased glomerular albumin permeability (P alb ) in a model of type 1 diabetes. Male SD rats (250‐275 g) were given streptozotocin (diabetic, D; i.v., 65 mg/kg) or saline (S). Half of each group received the ET A ‐selective antagonist, ABT‐627 (ABT), in drinking water at 5 mg/kg/d (n=6 in all groups). Treatment was begun immediately after confirming plasma glucose >300 mg/dl. Six weeks later, glomeruli were isolated by sieving techniques and P alb determined from the change in glomerular volume induced by exposing glomeruli to oncotic gradients of albumin. P alb was increased in D (0.91 ±0.09 vs. S, 0.05 ±0.01, P <0.01); ABT significantly reduced P alb when compared with D (D+ABT, 0.40 ±0.10, P <0.05). ABT had no effect on P alb in S rats. Acute in vitro incubation of glomeruli isolated from D with ABT (10 −6 M, 15 min at 37°C), significantly reduced P alb (0.89±0.11 to 0.41±0.09, P <0.05) while selective ET B blockade, A192621 (10 −3 to 10 −7 M), had no effect. In conclusion, these data support the hypothesis that ET A but not ET B receptors play an important role in maintaining elevated P alb in type 1 diabetes. Mechanisms responsible for additional changes not affected by ABT remain to be determined.