Abstract
GLP-1 is a new type of antidiabetic agent that possesses many beneficial effects. Although its cardiovascular actions have been widely examined, little is known about GLP-1's effects on the rat coronary artery (RCA) or about the mechanisms underpinning these effects. Here, we report that GLP-1 inhibits depolarization- or thromboxane receptor agonist (U46619)-induced RCA contraction in a dosage-dependent manner. Vasorelaxation was attenuated by denuding the endothelium, L-NAME (nitric oxide synthase inhibitor), and glyburide (KATP channel blocker) but was not affected by indomethacin (cyclooxygenase inhibitor), iberiotoxin [Ca2+-activated K+ channel (KCa) blocker], or 4-aminopyridine (KV channel blocker). Furthermore, GLP-1 increased outward K+ currents by enhancing the KATP channel in rat coronary arterial smooth muscle cells (RCASMCs). These results show that GLP-1 is an endothelial-dependent vasospasmolytic agent in the RCA and imply that the relaxant effect is regulated by enhancing KATP rather than KV or KCa currents in RCASMCs.
Highlights
Glucagon-like peptide-1 (GLP-1) is an incretin synthesized and secreted by intestinal L cells and a peptide that binds to its GLP-1 receptor (GLP-1R) to regulate glucose homeostasis by stimulating insulin secretion in a glucose-dependent manner
We investigated the potential vasorelaxant effects of GLP-1 on the rat coronary artery and examined the mechanisms underlying these effects by investigating the impact of GLP-1 on the KATP currents in rat coronary arterial smooth muscle cells (RCASMCs)
GLP-1 was synthesized by Sangon Biotech, and NG-nitro-L-arginine methylester ester (L-NAME), indomethacin, 4-aminopyridine (4-AP), glyburide (Glyb), iberiotoxin (Iber), 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U46619), and HEPES were purchased from Sigma
Summary
Glucagon-like peptide-1 (GLP-1) is an incretin synthesized and secreted by intestinal L cells and a peptide that binds to its GLP-1 receptor (GLP-1R) to regulate glucose homeostasis by stimulating insulin secretion in a glucose-dependent manner. Accumulating studies suggest that GLP-1 plays a cardioprotective role by regulating glucose uptake and left ventricular function [2]. E LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial demonstrated that, beyond its original role as an antidiabetic agent, the GLP-1 receptor agonist liraglutide exerts a blood pressure-lowering effect in addition to reducing the cardiovascular disease risk [3]. Experimental evidence on the ex vivo vascular actions has revealed that GLP-1 (7–36), an active isoform of GLP-1, exerts a vasorelaxant action on different types of blood vessels, such as the rat thoracic aorta [5, 6], porcine ileal artery [7], rat pulmonary artery [8], and femoral artery [9]
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