Protective Effects of Glucagon-like Peptide 1 on Endothelial Function in Hypertension.
Vascular endothelial cells play a major role in maintaining cardiovascular homeostasis. Endothelial dysfunction, characterized by reduced endothelium-dependent relaxations or accompanied by enhanced endothelium-dependent contractions, is a hallmark of and plays a pivotal role in the pathogenesis of hypertension. Endothelial dysfunction in hypertension has been linked to decreases in nitric oxide (NO) bioavailability, reflecting the impaired generation of NO and/or the enhanced inactivation of NO by reactive oxygen species. Many of these conditions can be improved by glucagon-like peptide 1 (GLP-1), a proglucagon-derived hormone secreted by intestinal endocrine L-type cells, which is rapidly inactivated by an enzyme dipeptidyl peptidase 4 in circulation. On one hand, GLP-1 analogues or dipeptidyl peptidase 4 inhibitors upregulate endothelial nitric oxide synthase expression and increase endothelial nitric oxide synthase phosphorylation, resulting in improved production of NO and thus endothelium-dependent relaxations. On the other hand, GLP-1 and related agents attenuate endothelium-dependent contractions by reducing reactive oxygen species generation and cyclooxygenase-2 expression. GLP-1 elevating agents and GLP-1 receptor agonists improve endothelial function in hypertension, suggesting that GLP-1 signaling could be a therapeutic target in hypertension-related vascular events.
*Department of Physiology and Pathophysiology, Peking University Health Science Center, Peking, China; and †Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
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D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052216:Glucagon-Like Peptide 1; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2