Propylthiouracil-induced hypothyroidism is associated with increased tolerance of the isolated rat heart to ischaemia-reperfusion.
The present study investigated the response of the hypothyroid heart to ischaemia-reperfusion. Hypothyroidism was induced in Wistar rats by oral administration of propylthiouracil (0.05%) for 3 weeks (HYPO rats), while normal animals (NORM) served as controls. Isolated hearts from NORM and HYPO animals were perfused in Langendorff mode and subjected to zero-flow global ischaemia followed by reperfusion (I/R). Post-ischaemic recovery of left ventricular developed pressure was expressed as % of the initial value (LVDP%). Basal expression of protein kinase C epsilon (PKCepsilon) and PKCdelta and phosphorylation of p46 and p54 c-jun NH(2)-terminal kinases (JNKs) in response to I/R were assessed by Western blotting. LVDP% was found to be significantly higher in HYPO hearts than in NORM. At baseline, PKCepsilon expression was 1.4-fold more in HYPO than in NORM hearts, P<0.05, while PKCdelta was not changed. Furthermore, basal phospho-p54 and -p46 JNK levels were 2.2- and 2.6-fold more in HYPO than in NORM hearts, P<0.05. In response to I/R, in NORM hearts, phospho-p54 and -p46 JNK levels were 5.5- and 6.0-fold more as compared with the baseline values, P<0.05, while they were not significantly altered in HYPO hearts. HYPO hearts seem to display a phenotype of cardioprotection against ischaemia-reperfusion and this is associated with basal PKCepsilon overexpression and attenuated JNK activation after I/R.
Pantos
C
C
Department of Pharmacology, University of Athens, 75 Mikras Asias Avenue, 11527 Goudi, Athens, Greece. cpantos@cc.uoa.gr
Malliopoulou
V
V
Mourouzis
I
I
Sfakianoudis
K
K
Tzeis
S
S
Doumba
P
P
Xinaris
C
C
Cokkinos
A D
AD
Carageorgiou
H
H
Varonos
D D
DD
Cokkinos
D V
DV
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D007037:Hypothyroidism / Q000150:complications* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000032:analysis / Q000378:metabolism; D023421:Models, Animal; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D010766:Phosphorylation; D011441:Propylthiouracil; D011493:Protein Kinase C / Q000378:metabolism; D051744:Protein Kinase C-epsilon; D051381:Rats; D017208:Rats, Wistar; D017725:Ventricular Pressure
D011441:Propylthiouracil; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases