학술논문
GLP-1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading.
Document Type
Academic Journal
Author
Haddock B; Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.; Kristensen KB; Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.; Tayyab M; Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.; Larsson HBW; Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.; Lindberg U; Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.; Vestergaard M; Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.; Francis S; Sir Peter Mansfield Magnetic Resonance Centre School of Physics and Astronomy University of Nottingham United Kingdom.; Jensen BL; Department of Cardiovascular and Renal Research, Institute of Molecular Medicine University of Southern Denmark Odense Denmark.; Andersen UB; Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.; Asmar A; Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.; Department of Clinical Physiology and Nuclear Medicine, Bispebjerg and Frederiksberg Hospital Copenhagen University Hospital Copenhagen Denmark.; Department of Clinical Medicine University of Copenhagen Copenhagen Denmark.
Source
Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101580524 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2047-9980 (Electronic) Linking ISSN: 20479980 NLM ISO Abbreviation: J Am Heart Assoc Subsets: MEDLINE
Subject
Language
English
Abstract
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.