Neumann Joachim, Hadová Katarína, Klimas Jan, Hofmann Britt, Gergs Ulrich
Institute for Pharmacology and Toxicology, Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Straße 4, D-06112 Halle (Saale), Germany.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, SK-83232 Bratislava, Slovakia.
Pharmaceutics. 2024 Aug 28;16(9):1139. doi: 10.3390/pharmaceutics16091139.
Semaglutide is a glucagon-like peptide 1 receptor (GLP-1R) agonist. GLP-1R agonists are used to treat type 2 diabetes and obesity. It is currently unknown whether semaglutide can directly increase force of contraction (FOC) in the human heart. We tested the hypothesis that semaglutide might increase the FOC in the isolated human atrium. To this end, we conducted contraction experiments in isolated human right atrial muscle preparations (HAP). HAP were obtained during open-heart surgery. We detected a concentration- and time-dependent positive inotropic effect (PIE) of semaglutide in HAP. These PIEs were accompanied by increases in the rates of tension development and tension relaxation and a reduction in muscle relaxation time. The PIE of semaglutide in HAP was attenuated by H89, an inhibitor of the cyclic AMP-dependent protein kinase and by ryanodine, an inhibitor of sarcoplasmic Ca release. Semaglutide up to 100 nM failed to exert a PIE in isolated electrically paced (1 Hz) wild-type mouse left atrial preparations studied for comparison. Our data suggest that semaglutide can increase the FOC in the atria of patients at therapeutic drug concentrations.
司美格鲁肽是一种胰高血糖素样肽-1受体（GLP-1R）激动剂。GLP-1R激动剂用于治疗2型糖尿病和肥胖症。目前尚不清楚司美格鲁肽是否能直接增加人类心脏的收缩力（FOC）。我们测试了司美格鲁肽可能增加离体人心房FOC的假设。为此，我们在离体人右心房肌标本（HAP）中进行了收缩实验。HAP是在心脏直视手术期间获得的。我们在HAP中检测到了司美格鲁肽浓度和时间依赖性的正性肌力作用（PIE）。这些PIE伴随着张力发展速率和张力松弛速率的增加以及肌肉松弛时间的缩短。H89（一种环磷酸腺苷依赖性蛋白激酶抑制剂）和兰尼碱（一种肌浆网钙释放抑制剂）可减弱司美格鲁肽在HAP中的PIE。为作比较，在研究的离体电起搏（1Hz）野生型小鼠左心房标本中，高达100nM的司美格鲁肽未能发挥PIE。我们的数据表明，在治疗药物浓度下，司美格鲁肽可增加患者心房的FOC。
