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Cardioprotective effect of thyroid hormone is mediated by AT2 receptor and involves nitric oxide production via Akt activation in mice

Item Type:Article
Title:Cardioprotective effect of thyroid hormone is mediated by AT2 receptor and involves nitric oxide production via Akt activation in mice
Creators Name:da Silva, I.B., Gomes, D.A., Alenina, N., Bader, M., dos Santos, R.A. and Barreto-Chaves, M.L.M.
Abstract:Studies have demonstrated that thyroid hormone (T3) can precondition the heart against ischaemic injury and improve post-ischaemic recovery. This study investigated whether the AT2 receptor (AT2R) is involved in cardioprotection and the potential molecular mechanism responsible for this effect. Hyperthyroidism was induced in male wild-type (WT) and AT2R knockout (KO) mice by administering daily intraperitoneal injections of T3 (7 μg/100 g body weight) for 14 days. The mouse hearts were harvested and perfused with a Krebs-Henseleit solution at a constant flow in a Langendorff set-up. After 30 min of stabilization, the hearts were subjected to global ischaemia for 20 min and reperfused for 45 min. Baseline cardiac function was assessed by measuring four parameters: LVDP (mmHg), heart rate (bpm), + dP/dt and - dP/dt (mmHg/s). After reperfusion, the total protein from cardiac ventricles was obtained, and the Akt signalling pathway and NO production were evaluated. Post-ischaemic functional recovery was significantly greater (p < 0.05) in the T3-treated WT mice compared to the control, demonstrating the cardioprotective effect of T3. This effect was abolished in T3-treated KO mice, demonstrating the physiological relevance of AT2R to the cardioprotective phenotype induced by T3. Akt activation, iNOS expression and NO production increased in cardiac tissue after T3 treatment in the WT animals, but no difference was observed after treatment in the KO mice. This study indicates that AT2R acts as a cardioprotector in the case of hyperthyroidism. Strategies targeting AT2R agonists might improve cardiac function through NO production and suggest potential therapeutic targets for heart diseases.
Keywords:Angiotensin II, Cardiac Hypertrophy, Cardioprotection, Isolated Heart Perfusion, Thyroid Hormone, Animals, Mice
Source:Heart and Vessels
Page Range:671-681
Date:June 2018
Official Publication:https://doi.org/10.1007/s00380-017-1101-5
PubMed:View item in PubMed

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