Glucagon‐like peptide‐1 receptor antagonism impairs basal exercise capacity and vascular adaptation to aerobic exercise training in rats

• Published in: Physiological reports Vol. 6; no. 13; pp. e13754 - n/a
• Main Authors: Scalzo, Rebecca L., Knaub, Leslie A., Hull, Sara E., Keller, Amy C., Hunter, Kendall, Walker, Lori A., Reusch, Jane E. B.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.07.2018; John Wiley and Sons Inc
• Subjects: Acetylcholine; Adaptation; Adaptation, Physiological; Aerobic capacity; Aerobics; Animals; Aorta; Aorta - metabolism; Aorta - physiology; Aortic strain; Cardiorespiratory Fitness; Cardiovascular diseases; Cardiovascular Physiology; Carotid Arteries - metabolism; Carotid Arteries - physiology; Corticotropin-releasing hormone; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Electron transport; Endocrine and Metabolic Conditons, Disorders and Treatments; Endurance and Performance; Exercise; Exercise Tolerance; Fitness training programs; Glucagon; Glucagon-Like Peptide-1 Receptor - antagonists & inhibitors; Heart; Male; Mitochondria; Mitochondria, Heart - metabolism; mitochondrial respiration; Mortality; Original Research; Peptide Fragments - pharmacology; Phenylephrine; Physical Conditioning, Animal; Physical fitness; Physiology; Rats; Rats, Wistar; Respiration; Rodents; Signalling Pathways; Vascular Stiffness; Vasoconstriction; Vasodilation; Ventricle; Aortic strain; vascular stiffness; mitochondrial respiration
• ISSN: 2051-817X
• DOI: 10.14814/phy2.13754

Cardiorespiratory fitness (CRF) inversely predicts cardiovascular (CV) mortality and CRF is impaired in people with type 2 diabetes (T2D). Aerobic exercise training (ET) improves CRF and is associated with decreased risk of premature death in healthy and diseased populations. Understanding the mechanisms contributing to ET adaptation may identify targets for reducing CV mortality of relevance to people with T2D. The antihyperglycemic hormone glucagon‐like peptide‐1 (GLP‐1) influences many of the same pathways as exercise and may contribute to CV adaptation to ET. We hypothesized that GLP‐1 is necessary for adaptation to ET. Twelve‐week‐old male Wistar rats were randomized (n = 8–12/group) to receive PBS or GLP‐1 receptor antagonist (exendin 9‐39 (Ex(9‐39)) via osmotic pump for 4 weeks ± ET. CRF was greater with ET (P < 0.01). Ex(9‐39) treatment blunted CRF in both sedentary and ET rats (P < 0.001). Ex(9‐39) attenuated acetylcholine‐mediated vasodilation, while this response was maintained with Ex(9‐39)+ET (P = 0.04). Aortic stiffness was greater with Ex(9‐39) (P = 0.057) and was made worse when Ex(9‐39) was combined with ET (P = 0.004). Ex vivo aortic vasoconstriction with potassium and phenylephrine was lower with Ex(9‐39) (P < 0.0001). Carotid strain improved with PBS + ET but did not change in the Ex(9‐39) rats with ET (P < 0.0001). Left ventricular mitochondrial respiration was elevated with Ex(9‐39) (P < 0.02). GLP‐1 receptor antagonism impairs CRF with and without ET, attenuates the vascular adaptation to ET, and elevates cardiac mitochondrial respiration. These data suggest that GLP‐1 is integral to the adaptive vascular response to ET. GLP‐1 receptor antagonism impairs exercise capacity, attenuates the vascular adaptation to exercise training, and elevates cardiac mitochondrial respiration. These data suggest that GLP‐1 is integral to the adaptive vascular response to exercise training.