Blockade of angiotensin II type 1 receptor diminishes cardiac hypertrophy, but does not abolish thyroxin-induced preconditioning.
Growth and stress seem to share common intracellular pathways and activation of growth signaling can increase resistance to stress. Thyroid hormone induces cardiac hypertrophy and preconditions the myocardium against ischemia reperfusion injury. The present study investigated whether this response is mediated by renin-angiotensin system (RAS). RAS is shown to be activated in hyperthyroidism and is involved in the development of cardiac hypertrophy. Male Wistar rats were treated with L-thyroxin (25 microg/100 g, sc, od) for fourteen days, while normal rats served as controls. In addition, irbesartan (150 mg/kg po), a potent blocker of angiotensin II type 1 receptor (AT1), was given with L-thyroxin for fourteen days. Isolated hearts were perfused in Langendorff mode; after stabilization, they were subjected to 20 min zero-flow global ischemia and 45 min of reperfusion. Thyroxin induced cardiac hypertrophy, which was diminished with irbesartan administration. Post-ischemic recovery of function was increased in thyroxin-treated hearts as compared to controls while ischemic contracture was accelerated and intensified. Irbesartan did not abolish this response. In conclusion, blockade of angiotensin II type 1 receptor with irbesartan preserves thyroxin-induced cardioprotection while diminishing cardiac hypertrophy. It is likely that thyroxin-induced cardioprotection is due to a direct effect of thyroid hormone.
Pantos
C
C
Department of Pharmacology, University of Athens, Athens, Greece. cpantos@cc.uoa.gr
Paizis
I
I
Mourouzis
I
I
Moraitis
P
P
Tzeis
S
S
Karamanoli
E
E
Mourouzis
C
C
Karageorgiou
H
H
Cokkinos
D V
DV
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D006332:Cardiomegaly / Q000178:diet therapy; D000077405:Irbesartan; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced / Q000503:physiopathology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System; D013777:Tetrazoles / Q000008:administration & dosage*; D013974:Thyroxine / Q000008:administration & dosage*
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000077405:Irbesartan; D013974:Thyroxine