The effects of chronic candesartan treatment on cardiac and hepatic adenosine monophosphate-activated protein kinase in rats submitted to surgical stress.
BACKGROUND
adenosine monophosphate-activated protein kinase (AMPK) plays a prominent role as a metabolic stress sensor, and it has recently been suggested that the renin-angiotensin system, in addition to its role in stress regulation, may play a significant role in regulating the AMPK system. This study aimed to evaluate the effects of candesartan, an angiotensin II receptor blocker, on cardiac and hepatic AMPK activity basally as well as after surgical stress under general anesthesia.


METHODS
Male Wistar rats were treated with 5 mg/kg/day candesartan in their drinking water for two weeks. Levels of cardiac and hepatic AMPK activity were determined, using a kinase activity assay, basally and after surgical stress under general anesthesia.


RESULTS
Chronic administration of candesartan increased hepatic AMPK activity approximately 4 times (p<0.05) while no significant change was demonstrated in cardiac AMPK. Cardiac and hepatic AMPK activities were not significantly increased by surgical stress alone performed under anesthesia. However, chronic treatment with candesartan decreased AMPK activity in both liver and heart after surgical stress under anesthesia (p<0.01 for both comparisons).


CONCLUSIONS
While chronic candesartan treatment may stimulate AMPK activity in certain organs such as the liver, when combined with surgical stress under anesthesia it inhibits pathways regulating AMPK activity.
Department of Internal Medicine, Federal University of Minas Gerais, Brazil.
Antônio
A
Ribeiro-Oliveira
Department of Internal Medicine, Federal University of Minas Gerais, Brazil Department of Endocrinology, Queen Mary University of London, UK.
Mirna B
MB
Marques
Department of Surgery, Federal University of Minas Gerais, Brazil.
Walkiria W
WW
Vilas-Boas
Department of Internal Medicine, Federal University of Minas Gerais, Brazil.
Jonas
J
Guimarães
Department of Physiology and Biophysics, Federal University of Minas Gerais, Brazil.
Cândido C
CC
Coimbra
Department of Internal Medicine, Federal University of Minas Gerais, Brazil.
Allan P
AP
Anjos
Department of Internal Medicine, Federal University of Minas Gerais, Brazil.
Rodrigo B
RB
Fóscolo
Department of Physiology and Biophysics, Federal University of Minas Gerais, Brazil.
Robson
R
Santos
Department of Endocrinology, Queen Mary University of London, UK.
Julia D
JD
Thomas
Department of Endocrinology, Queen Mary University of London, UK.
Suzana M
SM
Igreja
Department of Endocrinology, Queen Mary University of London, UK.
Blerina
B
Kola
Department of Endocrinology, Queen Mary University of London, UK Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, UK.
Ashley B
AB
Grossman
Department of Endocrinology, Queen Mary University of London, UK m.korbonits@qmul.ac.uk.
Márta
M
Korbonits
D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001713:Biphenyl Compounds; D007813:Laparotomy; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000263:Adenylate Kinase; C081643:candesartan
AMP-activated protein kinase; angiotensin receptor blocker; candesartan; stress; surgery