Experimental hyperthyroidism increases expression of parathyroid hormone-related peptide and type-1 parathyroid hormone receptor in rat ventricular myocardium of the Langendorff ischaemia-reperfusion model

摘要

Parathyroid hormone-related peptide (PTHrP) is released under ischaemic conditions and it improves contractile function of stunned myocardium. The actions of PTHrP are mediated primarily by the type 1 parathyroid hormone receptor (PTH.1R), while PTHrP and PTH.1R expression levels are increased in ventricular hypertrophy associated with experimental hyperthyroidism. Since chronic administration of thyroxine (T_4) improves postischaemic recovery in isolated heart models subjected to ischaemia-reperfusion stress, we tested the hypothesis that experimentally induced hyperthyroidism is associated with elevated expression of PTHrP and PTH.1R in rat myocardium. Hyperthyroid and control male Wistar rats were subjected to ischaemia-reperfusion stress using the Langendorff technique, and the PTHrP and PTH.1R expression was assessed by relative quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis and immunohistochemistry. In the Langendorff model, the recovery of left ventricular developed pressure at the end of the stablization period and 45 min into the reperfusion period was used to assess the cardioprotective actions of T_4 administration. Our data show that hyperthyroid animals had increased tolerance to the ischaemia-reperfusion stress and that this was associated with an increase of PTHrP and PTH.1R expression levels compared with those of control animals. In the control animals, the expression of PTHrP was increased 45 min into the reperfusion phase, while the PTH.1R expression pattern was significantly and gradually decreased throughout the ischaemia and reperfusion phases. In the hyperthyroid animals, the PTHrP and PTH.1R expression pattern was significantly higher throughout the ischaemia and reperfusion phases compared with that of control hearts. Our data suggest that increasing levels of PTHrP and PTH.1R expression can mediate, at least in part, the T_4 administration-induced cardioprotection in rat ventricular myocardium.