GLP-1 Relaxes Rat Coronary Arteries by Enhancing ATP-Sensitive Potassium Channel Currents.

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 (K_ATP channel blocker) but was not affected by indomethacin (cyclooxygenase inhibitor), iberiotoxin [Ca²⁺-activated K⁺ channel (K_Ca) blocker], or 4-aminopyridine (K_V channel blocker). Furthermore, GLP-1 increased outward K⁺ currents by enhancing the K_ATP 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 K_ATP rather than K_V or K_Ca currents in RCASMCs.