Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old ratsстатья

Статья опубликована в высокорейтинговом журнале

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Дата последнего поиска статьи во внешних источниках: 17 октября 2017 г.

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[1] Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats / S. I. Sofronova, D. K. Gaynullina, A. A. Shvetsova et al. // Journal of Endocrinology. — 2017. — Vol. 235, no. 2. — P. 137–151. The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO-pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU-pups, compared to controls, demonstrated smaller maximum response to α1-adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by L-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both L-NNA effects were impaired in PTU-pups. PTU-pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU-pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU-pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to L-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood. [ DOI ]

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