Antidiabetic Drug Alogliptin Protects the Heart Against Ischemia-reperfusion Injury Through GLP-1 Receptor-dependent and Receptor-independent Pathways Involving Nitric Oxide Production in Rabbits
| Autor: | Kenshi Higashi, Hiromitsu Kanamori, Shinya Baba, Yoshihisa Yamada, Kazuhiko Nishigaki, Shinya Minatoguchi, Shingo Minatoguchi, Masanori Kawasaki, Masamitsu Iwasa |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Cardiotonic Agents Ischemia Administration Oral Myocardial Reperfusion Injury 030204 cardiovascular system & hematology Pharmacology Nitric Oxide Glucagon-Like Peptide-1 Receptor Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Piperidines medicine Animals Hypoglycemic Agents Uracil Receptor Glucagon-like peptide 1 receptor Ejection fraction digestive oral and skin physiology Heart medicine.disease 030104 developmental biology chemistry Coronary occlusion Rabbits Cardiology and Cardiovascular Medicine Reperfusion injury Alogliptin Signal Transduction |
| Zdroj: | Journal of Cardiovascular Pharmacology. 70:382-389 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/fjc.0000000000000531 |
| Popis: | GLP-1 has been reported to be cardioprotective against ischemia-reperfusion injury. We aimed to examine the effect of alogliptin, which may produce GLP-1, on ischemia-reperfusion injury and its mechanisms. Rabbits were fed a normal chow (control group) and a chow containing alogliptin (2 mg·kg·d: alogliptin-L group and 20 mg·kg·d: alogliptin-H group) for 7 days. The rabbits underwent 30 minutes of coronary occlusion and 48 hours of reperfusion. Exendin (9-39) [5 or 50 μg/kg, i.v., alogliptin-H+exendin (9-39)-L group and alogliptin-H+exendin (9-39)-H group] or L-NAME (10 mg/kg, i.v., alogliptin-H+L-NAME group) was administered to the alogliptin-H group. Alogliptin dose-dependently reduced the infarct size, which was partially blocked by exendin (9-39), but completely blocked by L-NAME. Exendin (9-39) or L-NAME alone did not affect the infarct size for themselves. The left ventricular ejection fraction and ±dP/dt were higher in the alogliptin-L group and alogliptin-H group than in the control group. Alogliptin increased the serum NOx and plasma GLP-1 levels, and those levels inversely correlated with the infarct size. Alogliptin upregulated the expressions of phosphorylated (p)-Akt and p-eNOS, which were inhibited by exendin (9-39) and L-NAME, respectively. In conclusion, alogliptin protects the heart against ischemia-reperfusion injury through GLP-1 receptor-dependent and receptor-independent pathways which involve nitric oxide production in rabbits. |
| Databáze: | OpenAIRE |
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