Insulin alone or with captopril: effects on signaling pathways (AKT and AMPK) and oxidative balance after ischemia-reperfusion in isolated hearts.
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.
Laboratory of Cardiovascular Physiology, Department of Physiology, ICBS, UFRGS, Porto Alegre, RS, Brazil. biraoliveira@yahoo.com
Ubirajara Oliveira
UO
de Oliveira
Adriane
A
Belló-Kein
Álvaro Reischak
ÁR
de Oliveira
Luiz Carlos
LC
Kuchaski
Ubiratan Fabres
UF
Machado
Maria Claudia
MC
Irigoyen
Beatriz D'Agord
BD
Schaan
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000378:metabolism* / Q000517:prevention & control; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015398:Signal Transduction
D000975:Antioxidants; D002316:Cardiotonic Agents; D007328:Insulin; D002216:Captopril; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases