GLP-1 Receptor Agonist Exenatide Increases Capillary Perfusion Independent of Nitric Oxide in Healthy Overweight Men. Issue 6 (June 2015)

• Record Type: Journal Article
• Authors: Smits, Mark M.; Muskiet, Marcel H.A.; Tonneijck, Lennart; Kramer, Mark H.H.; Diamant, Michaela; van Raalte, Daniël H.; Serné, Erik H.
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 35:Issue 6(2015)
• Publication Date: 2015-06
• Subjects: capillaries -- glucagon-like peptide-1 -- nitric oxide; Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.115.305447
• Languages: English
• ISSNs: 1079-5642

Abstract

Abstract : Objective—: The insulinotropic gut–derived hormone glucagon-like peptide-1 (GLP-1) increases capillary perfusion via a nitric oxide–dependent mechanism in rodents. This improves skeletal muscle glucose use and cardiac function. In humans, the effect of clinically used GLP-1 receptor agonists (GLP-1RAs) on capillary density is unknown. We aimed to assess the effects of the GLP-1RA exenatide on capillary density as well as the involvement of nitric oxide in humans. Approach and Results—: We included 10 healthy overweight men (age, 20–27 years; body mass index, 26–31 kg/m 2 ). Measurements were performed during intravenous infusion of placebo (saline 0.9%), exenatide, and a combination of exenatide and the nonselective nitric oxide–synthase inhibitor L- N G -monomethyl arginine. Capillary videomicroscopy was performed, and baseline and postocclusive (peak) capillary densities were counted. Compared with placebo, exenatide increased baseline and peak capillary density by 20.1% and 8.3%, respectively (both P =0.016). Concomitant L- N G -monomethyl arginine infusion did not alter the effects of exenatide. Vasomotion was assessed using laser Doppler fluxmetry. Exenatide nonsignificantly reduced the neurogenic domain of vasomotion measurements ( R =−5.6%; P =0.092), which was strongly and inversely associated with capillary perfusion ( R =−0.928; P =0.036). Glucose levels were reduced during exenatide infusion, whereas levels of insulin were unchanged. Conclusions—: Acute exenatide infusion increases capillary perfusion via nitric oxide–independent pathways in healthy overweight men, suggesting direct actions of this GLP-1RA on microvascular perfusion or interaction with vasoactive factors. Abstract : Supplemental Digital Content is available in the text.