Voluntary exercise training restores anticontractile effect of NO in coronary arteries of adult rats with antenatal/early postnatal hypothyroidism

• Published in: Nitric oxide Vol. 74; pp. 10 - 18
• Main Authors: Gaynullina, D.K., Borzykh, A.A., Sofronova, S.I., Selivanova, E.K., Shvetsova, A.A., Martyanov, A.A., Kuzmin, I.V., Tarasova, O.S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2018
• Subjects: 6-Propyl-2-thiouracil; Animals; Coronary arteries; Coronary Vessels - drug effects; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Exercise Test; Female; Hypothyroidism; Hypothyroidism - drug therapy; Hypothyroidism - physiopathology; Male; Muscle Contraction - drug effects; Nitric oxide; Nitric Oxide - pharmacology; Physical Conditioning, Animal; Rats; Rats, Wistar; Voluntary exercise; 6-Propyl-2-thiouracil; NO; d100; L-NNA; DEA/NO; Hypothyroidism; Endothelium; AUC; PTU; NOS; Nitric oxide; EC50; Voluntary exercise; Coronary arteries; pD2
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2018.01.001

Our recent study showed that NO-mediated anticontractile effect of endothelium is absent in coronary arteries of adult rats, which suffered from antenatal/early postnatal hypothyroidism. This study tested the hypothesis that exercise training would improve such detrimental consequences of early thyroid deficiency.
Wistar dams received propylthiouracil (PTU, 7 ppm) in drinking water during gestation and two weeks postpartum; control dams received tap water. Six-week-old male offspring of control (CON) and PTU dams was divided into sedentary (CON-Sed, n = 12; PTU-Sed, n = 10) and trained (CON-Tr, n = 12; PTU-Tr, n = 10) groups; the latter had 24-h access to running wheels. Eight weeks later coronary arteries were studied by wire myography. Anticontractile effect of NO was assessed by the effects of NOS inhibitor L-NNA on the basal tone and contractile response to U46619. Oxidative phosphorylation complexes and eNOS were estimated by Western blotting.
T3/T4 and TSH levels (ELISA) were normalized in the progeny of PTU-treated dams at the age of 6 weeks and were not affected by training. Total running distance did not differ between CON-Tr and PTU-Tr. The contents of oxidative phosphorylation complexes were increased post-training in triceps brachii muscle from CON-Tr and PTU-Tr and in heart from PTU-Tr. Coronary arteries of PTU-Sed compared to CON-Sed demonstrated higher basal tone and contractile response to U46619, which were not further increased by L-NNA. The effects of L-NNA on the basal tone and contractile response to U46619 did not differ in CON-Tr and PTU-Tr groups, but were elevated in PTU-Tr compared to PTU-Sed group. PTU-Tr rats in comparison to PTU-Sed group had higher eNOS content in heart. Responses of coronary arteries to DEA/NO did not differ among all experimental groups.
Long-lasting coronary endothelial dysfunction resulted from transient thyroid deficiency during the antenatal/early postnatal period can be corrected by voluntary exercise training.
•Antenatal hypothyroidism weakens NO effects in coronary arteries of adult rats.•Exercise increases OXPHOS and eNOS in myocardium of previously hypothyroid rats.•Exercise improves anticontractile effects of NO in previously hypothyroid rats.