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GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading
BACKGROUND: GLP‐1 (glucagon‐like peptide‐1) receptor agonists exert beneficial long‐term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP‐1 depends on GLP‐1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in r...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9973647/ https://www.ncbi.nlm.nih.gov/pubmed/36734354 http://dx.doi.org/10.1161/JAHA.122.027712 |
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author | Haddock, Bryan Kristensen, Kasper B. Tayyab, Mahvish Larsson, Henrik B. W. Lindberg, Ulrich Vestergaard, Mark Francis, Susan Jensen, Boye L. Andersen, Ulrik B. Asmar, Ali |
author_facet | Haddock, Bryan Kristensen, Kasper B. Tayyab, Mahvish Larsson, Henrik B. W. Lindberg, Ulrich Vestergaard, Mark Francis, Susan Jensen, Boye L. Andersen, Ulrik B. Asmar, Ali |
author_sort | Haddock, Bryan |
collection | PubMed |
description | BACKGROUND: GLP‐1 (glucagon‐like peptide‐1) receptor agonists exert beneficial long‐term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP‐1 depends on GLP‐1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP‐1 increases renal medullary perfusion in healthy humans. METHODS AND RESULTS: Healthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1‐hour infusion of either GLP‐1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R(2)*), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP‐1 infusion increased medullary perfusion (32±7%, P<0.001) and cortical perfusion (13±4%, P<0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (−5±2%, P=0.007), whereas cortical perfusion remained unchanged. R(2)* values increased by 3±2% (P=0.025) in the medulla and 4±1% (P=0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP‐1. Blood flow in the renal artery was not altered significantly by either intervention. CONCLUSIONS: GLP‐1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP‐1 may account for the increase in regional perfusion. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04337268. |
format | Online Article Text |
id | pubmed-9973647 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99736472023-03-01 GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading Haddock, Bryan Kristensen, Kasper B. Tayyab, Mahvish Larsson, Henrik B. W. Lindberg, Ulrich Vestergaard, Mark Francis, Susan Jensen, Boye L. Andersen, Ulrik B. Asmar, Ali J Am Heart Assoc Original Research BACKGROUND: GLP‐1 (glucagon‐like peptide‐1) receptor agonists exert beneficial long‐term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP‐1 depends on GLP‐1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP‐1 increases renal medullary perfusion in healthy humans. METHODS AND RESULTS: Healthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1‐hour infusion of either GLP‐1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R(2)*), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP‐1 infusion increased medullary perfusion (32±7%, P<0.001) and cortical perfusion (13±4%, P<0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (−5±2%, P=0.007), whereas cortical perfusion remained unchanged. R(2)* values increased by 3±2% (P=0.025) in the medulla and 4±1% (P=0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP‐1. Blood flow in the renal artery was not altered significantly by either intervention. CONCLUSIONS: GLP‐1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP‐1 may account for the increase in regional perfusion. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04337268. John Wiley and Sons Inc. 2023-02-03 /pmc/articles/PMC9973647/ /pubmed/36734354 http://dx.doi.org/10.1161/JAHA.122.027712 Text en © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Research Haddock, Bryan Kristensen, Kasper B. Tayyab, Mahvish Larsson, Henrik B. W. Lindberg, Ulrich Vestergaard, Mark Francis, Susan Jensen, Boye L. Andersen, Ulrik B. Asmar, Ali GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading |
title |
GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading |
title_full |
GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading |
title_fullStr |
GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading |
title_full_unstemmed |
GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading |
title_short |
GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading |
title_sort | glp−1 promotes cortical and medullary perfusion in the human kidney and maintains renal oxygenation during nacl loading |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9973647/ https://www.ncbi.nlm.nih.gov/pubmed/36734354 http://dx.doi.org/10.1161/JAHA.122.027712 |
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