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Insulin alone or with captopril: effects on signaling pathways (AKT and AMPK) and oxidative balance after ischemia–reperfusion in isolated hearts
Author(s) -
de Oliveira Ubirajara Oliveira,
BellóKein Adriane,
de Oliveira Álvaro Reischak,
Kuchaski Luiz Carlos,
Machado Ubiratan Fabres,
Irigoyen Maria Claudia,
Schaan Beatriz D’Agord
Publication year - 2012
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2011.00995.x
Subject(s) - captopril , medicine , endocrinology , angiotensin ii , insulin , ampk , protein kinase b , chemistry , ischemia , superoxide dismutase , renin–angiotensin system , protein kinase a , oxidative stress , pharmacology , phosphorylation , biochemistry , blood pressure
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.