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Sustained, delayed, and small increments in glomerular permeability to macromolecules during systemic ET-1 infusion mediated via the ETa receptor
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- Dolinina, Julia (author)
- Lund University,Lunds universitet,Njurfysiologi och peritonealdialys,Forskargrupper vid Lunds universitet,Renal physiology and peritoneal dialysis,Lund University Research Groups,Skåne University Hospital
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- Rippe, Anna (author)
- Lund University,Lunds universitet,Njurfysiologi och peritonealdialys,Forskargrupper vid Lunds universitet,Renal physiology and peritoneal dialysis,Lund University Research Groups,Skåne University Hospital
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- Öberg, Carl M. (author)
- Lund University,Lunds universitet,Njurfysiologi och peritonealdialys,Forskargrupper vid Lunds universitet,Renal physiology and peritoneal dialysis,Lund University Research Groups,Skåne University Hospital
- (creator_code:org_t)
- American Physiological Society, 2019
- 2019
- English.
- In: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 316:6, s. 1173-1179
- Journal article (peer-reviewed)
Abstract
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- Dolinina J, Rippe A, Öberg CM. Sustained, delayed, and small increments in glomerular permeability to macromolecules during systemic ET-1 infusion mediated via the ETA receptor. Am J Physiol Renal Physiol 316: F1173–F1179, 2019. First published March 13, 2019; doi:10.1152/ajprenal.00040.2019.—Emerging evidence indicates that endogenous production of endothelin (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 for neutral FITC-Ficoll (molecular Stokes-Einstein radius: 15–80 Å, molecular weight: 70 kDa/400 kDa) in anesthetized male Sprague-Dawley rats (n = 12) at baseline and at 5, 15, 30, and 60 min after intravenous administration of ET-1. In separate experiments, ET-1 was given together with the selective ET type A (ETA) or ET type B (ETB) receptor antagonists JKC-301 and BQ-788, respectively. At both 15 and 30 min postadministration, the glomerular sieving coefficient for macromolecular Ficoll (70 Å) was significantly increased to 4.4 x 10-5 0.7 x 10-5 (P = 0.024) and 4.5 x 10-5 0.8 x 10-5 (P = 0.007), respectively, compared with baseline (2.2 x 10-5 0.4 x10-5). Decreased urine production after ET-1 prevented the use of higher doses of ET-1. Data analysis using the two-pore model indicated changes in large-pore permeability after ET-1, with no changes in the small-pore pathway. Administration of ETA blocker abrogated the permeability changes induced by ET-1 at 30 min, whereas blockade of ETB receptors was ineffective. Mean arterial pressure was only significantly increased at 60 min, being 123 4 mmHg compared with 111 2 mmHg at baseline (P = 0.02). We conclude that ET-1 evoked small, delayed, and sustained increases in glomerular permeability, mediated via the ETA receptor.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
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