Evaluation of the Role of Glucagon-Like Peptide-1 Receptors in the Infarction-Limiting and Inotropic Effects of Adaptation to Chronic Hypoxia in Rats with and without Metabolic Syndrome.

We studied the involvement of glucagon-like peptide-1 receptors (GLP-1R) in mediating the infarct-limiting and inotropic effects of adaptation to chronic continuous hypoxia (CCH) in rats with normal metabolism and animals with diet-induced metabolic syndrome (MetS). CCH was modeled by housing rats in a hypoxic chamber (12% O2) continuously for 21 days. Acute myocardial ischemia/reperfusion was modeled by ligation of the left coronary artery for 45 min followed by reperfusion for 120 min. CCH resulted in a 44% reduction in infarct size during ischemia/reperfusion and improved myocardial contractility during reperfusion relative to the control group. MetS impaired the infarct-limiting and positive inotropic effects of CCH. Administration of the GLP-1R antagonist, exendin(9-39), at a dose of 50 μg/kg before modeling coronary occlusion had no effect on infarct size and cardiac contractility in rats adapted to CCH, in rats with MetS, or in rats adapted to CCH against the background of MetS. These results suggest that the GLP-1R is not involved in the infarct-limiting and positive inotropic effects of adaptation to CCH.