Sélley E, Kun S, Szijártó I A, Kertész M, Wittmann I, Molnár G A
2nd Department of Medicine and Nephrological Center University of Pécs, Pécs, Hungary.
Medical Clinic for Nephrology and Internal Intensive Care, Charité Campus Virchow Klinikum and Experimental and Clinical Research Center (ECRC), Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Horm Metab Res. 2016 Jul;48(7):476-483. doi: 10.1055/s-0042-101794. Epub 2016 Mar 14.
Glucagon is known for its insulin-antagonist effect in the blood glucose homeostasis, while it also reduces vascular resistance. The mechanism of the vasoactive effect of glucagon has not been studied before; thereby we aimed to investigate the mediators involved in the vasodilatation induced by glucagon. The vasoactive effect of glucagon, insulin, and glucagon-like peptide-1 was studied on isolated rat thoracic aortic rings using a wire myograph. To investigate the mechanism of the vasodilatation caused by glucagon, we determined the role of the receptor for glucagon and the receptor for GLP-1, and studied also the effect of various inhibitors of gasotransmitters, inhibitors of reactive oxygen species formation, NADPH oxidase, prostaglandin synthesis, protein kinases, potassium channels, and an inhibitor of the Na(+)/Ca(2+)-exchanger. Glucagon causes dose-dependent relaxation in the rat thoracic aorta, which is as potent as that of insulin but greater than that of GLP-1 (7-36) amide. Vasodilatation by GLP-1 is partially mediated by the glucagon receptor. The vasodilatation due to glucagon evokes via the glucagon-receptor, but also via the receptor for GLP-1, and it is endothelium-independent. Contribution of gasotransmitters, prostaglandins, the NADPH oxidase enzyme, free radicals, potassium channels, and the Na(+)/Ca(2+)-exchanger is also significant. Glucagon causes dose-dependent relaxation of rat thoracic aorta in vitro, via the receptor for glucagon and the receptor for GLP-1, while the vasodilatation evoked by GLP-1 also evolves partially via the receptor for glucagon, thereby, a possible crosstalk between the 2 hormones and receptors could occur.
胰高血糖素因其在血糖稳态中的胰岛素拮抗作用而闻名，同时它还能降低血管阻力。此前尚未研究过胰高血糖素血管活性作用的机制；因此，我们旨在研究参与胰高血糖素诱导的血管舒张的介质。使用线肌张力测定仪研究了胰高血糖素、胰岛素和胰高血糖素样肽 -1对离体大鼠胸主动脉环的血管活性作用。为了研究胰高血糖素引起血管舒张的机制，我们确定了胰高血糖素受体和GLP -1受体的作用，还研究了各种气体递质抑制剂、活性氧形成抑制剂、NADPH氧化酶、前列腺素合成、蛋白激酶、钾通道以及Na(+)/Ca(2+)-交换体抑制剂的作用。胰高血糖素可使大鼠胸主动脉产生剂量依赖性舒张，其效力与胰岛素相当，但大于GLP -1（7 - 36）酰胺。GLP -1引起的血管舒张部分由胰高血糖素受体介导。胰高血糖素引起的血管舒张通过胰高血糖素受体介导，但也通过GLP -1受体介导，且不依赖于内皮。气体递质、前列腺素、NADPH氧化酶、自由基、钾通道和Na(+)/Ca(2+)-交换体的作用也很显著。胰高血糖素在体外通过胰高血糖素受体和GLP -1受体使大鼠胸主动脉产生剂量依赖性舒张，而GLP -1引起的血管舒张也部分通过胰高血糖素受体发生，因此，这两种激素和受体之间可能存在相互作用。
