GLP-1 vasodilatation in humans with coronary artery disease is not adenosine mediated

• Published in: BMC cardiovascular disorders Vol. 21; no. 1; p. 223
• Main Authors: Aetesam-Ur-Rahman, Muhammad, Giblett, Joel P, Khialani, Bharat, Kyranis, Stephen, Clarke, Sophie J, Zhao, Tian X, Braganza, Denise M, Clarke, Sarah C, West, Nick E J, Bennett, Martin R, Hoole, Stephen P
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01-05-2021; BioMed Central; BMC
• Subjects: Adenosine; Adenosine - metabolism; Aged; Aged, 80 and over; Angina; Angina pectoris; Basal microvascular resistance (BMR); Blood vessels; Cardiovascular disease; Catheters; Causes of; Coronary artery; Coronary artery disease (CAD); Coronary Artery Disease - diagnosis; Coronary Artery Disease - metabolism; Coronary Artery Disease - physiopathology; Coronary heart disease; Coronary vessels; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Coronary Vessels - physiopathology; Demography; Development and progression; Diabetes; Diabetes mellitus; Dilatation; Female; Flow velocity; Glucagon; Glucagon-like peptide 1 (GLP-1); Glucagon-Like Peptide 1 - administration & dosage; Glucagon-like peptide 1 receptor agonists (GLP-1 RA); Health aspects; Heart attacks; Heart diseases; Humans; Hyperemia; Index of microvascular resistance (IMR); Male; Microvasculature; Middle Aged; Peptide hormones; Placebos; Purinergic P1 Receptor Antagonists - administration & dosage; Signal Transduction; Theophylline; Theophylline - administration & dosage; Vasodilation; Vasodilation - drug effects; Vasodilator Agents - administration & dosage; United Kingdom; United Kingdom > UK; Glucagon-like peptide 1 (GLP-1); Coronary artery disease (CAD); Index of microvascular resistance (IMR); Basal microvascular resistance (BMR); Glucagon-like peptide 1 receptor agonists (GLP-1 RA)
• ISSN: 1471-2261; 1471-2261
• DOI: 10.1186/s12872-021-02030-5

Incretin therapies appear to provide cardioprotection and improve cardiovascular outcomes in patients with diabetes, but the mechanism of this effect remains elusive. We have previously shown that glucagon-like peptide (GLP)-1 is a coronary vasodilator and we sought to investigate if this is an adenosine-mediated effect.
We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific study-related infusion following successful PCI: GLP-1 infusion (Group G) (n = 10); Placebo, normal saline infusion (Group P) (n = 11); GLP-1 + Theophylline infusion (Group GT) (n = 10); and Theophylline infusion (Group T) (n = 10). A pressure wire assessment of coronary distal pressure and flow velocity (thermodilution transit time-Tmn) at rest and hyperaemia was performed after PCI and repeated following the study infusion to derive basal and index of microvascular resistance (BMR and IMR).
There were no significant differences in the demographics of patients recruited to our study. Most of the patients were not diabetic. GLP-1 caused significant reduction of resting Tmn that was not attenuated by theophylline: mean delta Tmn (SD) group G - 0.23 s (0.27) versus group GT - 0.18 s (0.37), p = 0.65. Theophylline alone (group T) did not significantly alter resting flow velocity compared to group GT: delta Tmn in group T 0.04 s (0.15), p = 0.30. The resulting decrease in BMR observed in group G persisted in group GT: - 20.83 mmHg s (24.54 vs. - 21.20 mmHg s (30.41), p = 0.97. GLP-1 did not increase circulating adenosine levels in group GT more than group T: delta median adenosine - 2.0 ng/ml (- 117.1, 14.8) versus - 0.5 ng/ml (- 19.6, 9.4); p = 0.60.
The vasodilatory effect of GLP-1 is not abolished by theophylline and GLP-1 does not increase adenosine levels, indicating an adenosine-independent mechanism of GLP-1 coronary vasodilatation.
The local research ethics committee approved the study (National Research Ethics Service-NRES Committee, East of England): REC reference 14/EE/0018. The study was performed according to institutional guidelines, was registered on http://www.clinicaltrials.gov (unique identifier: NCT03502083) and the study conformed to the principles outlined in the Declaration of Helsinki.