NO-mediated anticontractile effect of the endothelium is abolished in coronary arteries of adult rats with antenatal/early postnatal hypothyroidism

Gaynullina, Dina; Софронова, С.И.; Selivanova, Ekaterina K; Shvetsova, Anastasia A.; Борзых, А. А.; Sharova, Anna; Kostyunina, Daria S; Martyanov, A. A.; Tarasova, O. S.

doi:10.1016/j.niox.2016.12.007

Cited by 16 publications

(23 citation statements)

References 33 publications

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“…Thyroid state is completely restored in adult rats suffered from antenatal/early postnatal hypothyroidism The results of the present study are consistent with our previous findings and show that treatment of dams with relatively low PTU dosage (7 ppm) causes significant reduction of thyroid hormones concentrations in their 2-week-old progeny, which, however, restores to adulthood. 9,10 Of note, already at the age of 6 weeks, the progeny of PTU-treated dams demonstrated restored blood levels of thyroid hormones and TSH, 20 which is consistent with other studies, where the restoration of thyroid state was observed in 4 weeks after PTU withdrawal. 8 Based on the above, we can consider that the adult rats from PTU group had an euthyroid status for at least 4 weeks before their arteries were taken for in vitro studies.…”

Section: Discussionsupporting

confidence: 90%

“…For example, antenatal/early postnatal hypothyroidism causes increased contractility of coronary vasculature in adult rats, despite the absence of evident alterations in their thyroid function and blood pressure level. 9 Further, antenatal/early postnatal hypothyroidism did not affect the responses of saphenous (cutaneous) artery but suppressed the activity of NO-pathway and increased procontractile effects of Rho-kinase in small mesenteric arteries of 2-week-old rat pups. 10 Importantly, our study 10 was the first to demonstrate the functional link between thyroid hormones and Rho-kinase pathway, a key regulator of smooth muscle contraction in vascular system.…”

Section: Introductionmentioning

confidence: 83%

“…7 On the other hand, high blood pressure does not always develop in adult progeny of hypothyroid rats. 8,9 The diversity of results suggests that there are adverse circulatory alterations only in certain organs, which might be more susceptible to the developmental thyroid deficiency than others. For example, antenatal/early postnatal hypothyroidism causes increased contractility of coronary vasculature in adult rats, despite the absence of evident alterations in their thyroid function and blood pressure level.…”

Section: Introductionmentioning

confidence: 99%

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Antenatal/early postnatal hypothyroidism increases the contribution of Rho-kinase to contractile responses of mesenteric and skeletal muscle arteries in adult rats

et al. 2018

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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Antenatal/early postnatal hypothyroidism increases the contribution of Rho-kinase to contractile responses of mesenteric and skeletal muscle arteries in adult rats

et al. 2018

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“…Of note, up to 15% of all pregnancies are accompanied by the overt or subclinical hypothyroidism (Stagnaro-Green 2015). Our recent findings show that antenatal/early postnatal hypothyroidism significantly alters the regulation of coronary circulation by abolishing the anticontractile effect of nitric oxide (NO) (Gaynullina et al 2017). Developmental effects of thyroid hormones on cardiovascular system are mediated by both genomic as well as nongenomic mechanisms, which may overlap at the nuclear level (Ojamaa 2010, Davis et al 2015.…”

Section: :2mentioning

confidence: 99%

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

Софронова

Gaynullina

Shvetsova

et al. 2017

Journal of Endocrinology

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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, and 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 α-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.

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“…Следует отметить, что сходные с хроническим гипотиреозом во взрослом возрасте изменения реактивности артерий были обнаружены нами при исследовании сосудистых ýффектов антенатального гипотиреоза, который также сопровождается увеличением сократительных от-ветов артерий икроножной мышцы и сердца во взрослом возрасте, через много недель после нормализации тиреоидного статуса [18,24]. Таким образом, дефицит тиреоидного влияния как в раннем периоде онтогенеза, так и во взрослом возрасте приводит к усилению роли Rho-киназы в регуляции сокращения.…”

Section: Discussionunclassified

Increase in the constrictor effects of Rho-kinase in skeletal muscle and coronary arteries of rats with chronic hypothyroidism

et al. 2018

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Aim. The deficit of thyroid function is known to be accompanied by an increase in the overall peripheral vascular resistance. This work tested the hypothesis that long-term hypothyroidism leads to an increase in the vasoconstrictor effect of Rho-kinase in skeletal muscle and heart resistance arteries of adult rats.Materials and methods.Male Wistar rats consumed the antithyroid drug propylthiouracil (PTU) in drinking water (0.025%), starting at 10 weeks of age. The rats of the control group received PTU-free water. After 14 weeks, the contractile responses of the gastrocnemius muscle arteries (to the α1-adrenoceptor agonist methoxamine) and the septal coronary artery (to the thromboxane A2 receptor agonist U46619) were isometrically recorded. The contribution of the Rho-kinase to the arterial contractile responses was assessed using inhibitor Y27632 (3 μM).Results.The consumption of propylthiouracil was accompanied by a marked decrease of thyroid hormone concentrations and an increase in total cholesterol serum level as well as a decrease in body weight. Maximal contractile responses of studied arteries were also reduced in hypothyroid rats. However, basal tone and reactivity to the moderate concentrations of agonists in arteries of hypothyroid rats were increased compared to control animals. Y27632 significantly weakened the contractile responses of the arteries and negated the differences between the two groups of rats.Conclusion.Chronic hypothyroidism leads to an increase in the activity of the Rho-kinase signaling pathway in the arteries of the gastrocnemius muscle and heart, which results in the increase of the spontaneous tone of the arteries and their reactivity to agonists.

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NO-mediated anticontractile effect of the endothelium is abolished in coronary arteries of adult rats with antenatal/early postnatal hypothyroidism

Cited by 16 publications

References 33 publications

Antenatal/early postnatal hypothyroidism increases the contribution of Rho-kinase to contractile responses of mesenteric and skeletal muscle arteries in adult rats

Antenatal/early postnatal hypothyroidism increases the contribution of Rho-kinase to contractile responses of mesenteric and skeletal muscle arteries in adult rats

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

Increase in the constrictor effects of Rho-kinase in skeletal muscle and coronary arteries of rats with chronic hypothyroidism

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