Sustained, delayed and small increments in glomerular permeability to macromolecules during systemic endothelin-1 infusion mediated via the ETA receptor.

Sustained, delayed and small increments in glomerular permeability to macromolecules during systemic endothelin-1 infusion mediated via the ETA receptor. Am J Physiol Renal Physiol. 2019 Mar 13;: Authors: Dolinina J, Rippe A, Öberg CM Abstract Emerging evidence indicates that endogenous production of endothelin 1 (ET-1), a 21-amino-acid peptide vasoconstrictor, plays an important role in proteinuric kidney disease. Previous studies in rats have shown that chronic administration of ET-1 leads to increased glomerular albumin leakage. The underlying mechanisms are however currently not known. Here we used size exclusion chromatography to measure glomerular sieving coefficients (θ) for neutral fluorescein isotiocyanate (FITC)-Ficoll (molecular Stokes-Einstein radius: 15-80 Å; MW 70 kDa/400kDa) in anesthetized male Sprague-Dawley rats (n=12) at baseline and at 5, 15, 30 and 60 minutes following intravenous administration of ET-1. In separate experiments, ET-1 was given together with a selective endothelin receptor A (ETA) or B (ETB) antagonist, JKC301 and BQ788, respectively. Both at 15 min and 30 min post-administration, θ for macromolecular Ficoll 70Å was significantly increased to 4.4·10-5± 0.7·10-5 (P=0.024) and 4.5·10-5± 0.8·10-5 (P=0.007), respectively, compared to baseline (2.2·10-5± 0.4·10-5). Decreased urine production following ET-1 prevented the use of higher doses of ET-1. Data analysis using the two-pore model i...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research