Insulin alone or with captopril: effects on signaling pathways (AKT and AMPK) and oxidative balance after ischemia-reperfusion in isolated hearts
| Autor: | Ubirajara Oliveira, de Oliveira, Adriane, Belló-Kein, Álvaro Reischak, de Oliveira, Luiz Carlos, Kuchaski, Ubiratan Fabres, Machado, Maria Claudia, Irigoyen, Beatriz D'Agord, Schaan |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Captopril Cardiotonic Agents Myocardium Blotting Western Drug Synergism Myocardial Reperfusion Injury AMP-Activated Protein Kinases In Vitro Techniques Antioxidants Rats Oxidative Stress Reperfusion Animals Insulin Lipid Peroxidation Rats Wistar Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Fundamentalclinical pharmacology. 26(6) |
| ISSN: | 1472-8206 |
| Popis: | Insulin and the inhibition of the renin-angiotensin system have independent benefits for ischemia-reperfusion injury, but their combination has not been tested. Our aim was to evaluate the effects of insulin+captopril on insulin/angiotensin signaling pathways and cardiac function in the isolated heart subjected to ischemia-reperfusion. Isolated hearts were perfused (Langendorff technique) with Krebs-Henseleit (KH) buffer for 25 min. Global ischemia was induced (20 min), followed by reperfusion (30 min) with KH (group KH), KH+angiotensin-I (group A), KH+angiotensin-I+captopril (group AC), KH+insulin (group I), KH+insulin+angiotensin-I (group IA), or KH+insulin+angiotensin-I+captopril (group IAC). Group A had a 24% reduction in developed pressure and an increase in end-diastolic pressure vs. baseline, effects that were reverted in groups AC, IA, and IAC. The phosphorylation of protein kinase B (AKT) was higher in groups I and IA vs. groups KH and A. The phosphorylation of AMP-activated protein kinase (AMPK) was ∼31% higher in groups I, IA, and IAC vs. groups KH, A, and AC. The tert-butyl hydroperoxide (tBOOH)-induced chemiluminescence was lower (∼2.2 times) in all groups vs. group KH and was ∼35% lower in group IA vs. group A. Superoxide dismutase content was lower in groups A, AC, and IAC vs. group KH. Catalase activity was ∼28% lower in all groups (except group IA) vs. group KH. During reperfusion of the ischemic heart, insulin activates the AKT and AMPK pathways and inhibits the deleterious effects of angiotensin-I perfusion on SOD expression and cardiac function. The addition of captopril does not potentiate these effects. |
| Databáze: | OpenAIRE |
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