Long-term thyroxine administration increases heat stress protein-70 mRNA expression and attenuates p38 MAP kinase activity in response to ischaemia

The present study was undertaken to investigate heat stress protein (HSP)-7 0 mRNA induction and p38 MAP kinase (MAPK) activity in response to ischaemi c stress in the hyperthyroid rat heart. L-Thyroxine (T-4) (25 mug/100g body weight) was administered to Wistar rats for 2 days (THYRacute) or 14 days (THYR), while animals treated similarly with normal saline served as controls (NORMacute and NORM). In addition, ab dominal aortic banding was performed in another group of rats to produce co nstriction-induced hypertrophy (HYP), while sham-operated (SOP) animals ser ved as controls. Isolated rat hearts were perfused in a Langendorff mode. H earts from NORMacute (n = 6), THYRacute animals (n = 8), NORM (n = 6), THYR (n = 6), SOP (n = 5) and HYP (n = 7) animals were subjected to 20 min of z ero-flow global ischaemia followed by 45 min of reperfusion. HSP70 mRNA exp ression and phosphorylated p38 MAPK protein expression were detected in res ponse to ischaemia and protein kinase C-epsilon (PKC epsilon) protein expre ssion was detected at baseline. Thyroid hormones were measured in plasma. Long-term T-4 administration and aortic constriction resulted in the develo pment of cardiac hypertrophy. Thyroid hormones were increased in both THYR and THYRacute as compared with normal groups (P < 005). HSP70 mRNA inductio n was increased 2.3-fold in THYR as compared with NORM hearts (P < 0.05), w hereas there was not any difference between THYRacute and NORMacute hearts (P > 0.05). Phosphorylated p38 MAPK protein expression was 22-fold more in NORM than in THYR hearts (P < 0.05), but it was not different between NORMa cute and THYRacute hearts (P > 0.05). HSP70 mRNA induction was 1.8-fold gre ater in HYP than in SOP hearts (P < 0.05), whereas phosphorylated p38 MAPK protein expression was similar between the two groups (P > 0.05). PKC epsil on protein expression at baseline was 1.7-fold more in NORM than in THYR he arts (P < 0.05), and not different between NORMacute and THYRacute hearts ( P > 0.05) as well as HYP and SOP hearts (P > 0.05). This study shows that HSP70 mRNA expression is increased, whereas p38 MAPK activation is attenuated in response to ischaemia in long-term T-4-treated rat hearts as compared with normal and acute hyperthyroid hearts.