TY - JOUR

T1 - GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading

AU - Haddock, Bryan

AU - Kristensen, Kasper B.

AU - Tayyab, Mahvish

AU - Larsson, Henrik B. W.

AU - Lindberg, Ulrich

AU - Vestergaard, Mark

AU - Francis, Susan

AU - Jensen, Boye L.

AU - Andersen, Ulrik B.

AU - Asmar, Ali

N1 - Publisher Copyright: © 2023 The Authors.

PY - 2023

Y1 - 2023

N2 - 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 low-ers 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 (R2 *), 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. R2 * 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.

AB - 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 low-ers 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 (R2 *), 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. R2 * 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.

KW - arterial spin labelling

KW - BOLD

KW - GLP-1

KW - kidney

KW - magnetic resonance imaging

KW - perfusion

KW - RBF

KW - renal

U2 - 10.1161/JAHA.122.027712

DO - 10.1161/JAHA.122.027712

M3 - Journal article

C2 - 36734354

AN - SCOPUS:85147536345

VL - 12

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 3

M1 - e027712

ER -