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

Muhammad Aetesam-ur-Rahman, Joel P. Giblett, Bharat Khialani, Stephen Kyranis, Sophie J. Clarke, Tian X. Zhao, Denise M. Braganza, Sarah C. Clarke, Nick E. J. West, Martin R. Bennett, Stephen P. Hoole
2020 unpublished
Background 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.Methods We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific
more » ... g 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).Results 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) vs. 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) vs. -0.5 ng/ml (-19.6, 9.4); p = 0.60.Conclusion 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..
doi:10.21203/rs.3.rs-42389/v1 fatcat:fsx7cndofjbhvphvibnquuo3ai