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

Gaynullina, Dina; Борзых, А. А.; Софронова, С.И.; Selivanova, Ekaterina K; Shvetsova, Anastasia A.; Martyanov, A. A.; Kuzmin, I. V.; Tarasova, O. S.

doi:10.1016/j.niox.2018.01.001

Cited by 9 publications

(9 citation statements)

References 43 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%

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%

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, the concentrations at which T4 or T3 are able to induce relaxation in vitro usually exceed their blood concentrations ( Zwaveling et al, 1997 ; Carrillo-Sepulveda et al, 2010 ; Cai et al, 2015 ; Lozano-Cuenca et al, 2016 ; Gaynullina et al, 2018a ). However, acute TH-induced vasorelaxation cannot be regarded as an experimental phenomenon only.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, stimulation of angiogenesis is predominantly induced by T4 and mediated by integrin αvβ3 (Bergh et al, 2005;Balzan et al, 2013;Liu et al, 2014). In addition, blood content of T4 is more than ten times higher compared to T3 content (Quesada et al, 2002;Ghasemi et al, 2013;Gaynullina et al, 2018a).…”

Section: Introductionmentioning

confidence: 99%

Thyroxine Induces Acute Relaxation of Rat Skeletal Muscle Arteries via Integrin αvβ3, ERK1/2 and Integrin-Linked Kinase

2021

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Aim: Hyperthyroidism is associated with a decreased peripheral vascular resistance, which could be caused by the vasodilator genomic or non-genomic effects of thyroid hormones (TH). Non-genomic, or acute, effects develop within several minutes and involve a wide tissue-specific spectrum of molecular pathways poorly studied in vasculature. We aimed to investigate the mechanisms of acute effects of TH on rat skeletal muscle arteries.Methods: Sural arteries from male Wistar rats were used for isometric force recording (wire myography) and phosphorylated protein content measurement (Western blotting).Results: Both triiodothyronine (T3) and thyroxine (T4) reduced contractile response of sural arteries to α1-adrenoceptor agonist methoxamine. The effect of T4 was more prominent than T3 and not affected by iopanoic acid, an inhibitor of deiodinase 2. Endothelium denudation abolished the effect of T3, but not T4. Integrin αvβ3 inhibitor tetrac abolished the effect of T4 in endothelium-denuded arteries. T4 weakened methoxamine-induced elevation of phospho-MLC2 (Ser19) content in arterial samples. The effect of T4 in endothelium-denuded arteries was abolished by inhibiting ERK1/2 activation with U0126 as well as by ILK inhibitor Cpd22 but persisted in the presence of Src- or Rho-kinase inhibitors (PP2 and Y27632, respectively).Conclusion: Acute non-genomic relaxation of sural arteries induced by T3 is endothelium-dependent and that induced by T4 is endothelium-independent. The effect of T4 on α1-adrenergic contraction is stronger compared to T3 and involves the suppression of extracellular matrix signaling via integrin αvβ3, ERK1/2 and ILK with subsequent decrease of MLC2 (Ser19) phosphorylation.

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“…However, several other studies utilizing different animal models have revealed that IUGR can lead to endothelial dysfunction by reducing the contribution of NO to the reactions of agonist-induced endothelium-dependent arterial relaxation 9 – 12 . Of note, such endothelium-dependent relaxations and anticontractile influence of endothelium (when endothelium counteracts vasocontraction via tonically released NO, see 33 ) represent two different aspects of endothelial functioning and can differentially change under pathologies affecting cardiovascular system 16 , 18 , 33 – 35 . Apparently, the same situation occurs in our IUGR model.…”

Section: Discussionmentioning

confidence: 99%

Intrauterine growth restriction weakens anticontractile influence of NO in coronary arteries of adult rats

Selivanova

Shvetsova

Shilova

et al. 2021

Sci Rep

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Intrauterine growth restriction (IUGR) is one of the most common pathologies of pregnancy. The cardiovascular consequences of IUGR do not disappear in adulthood and can manifest themselves in pathological alterations of vasomotor control. The hypothesis was tested that IUGR weakens anticontractile influence of NO and augments procontractile influence of Rho-kinase in arteries of adult offspring. To model IUGR in the rat, dams were 50% food restricted starting from the gestational day 11 till delivery. Mesenteric and coronary arteries of male offspring were studied at the age of 3 months using wire myography, qPCR, and Western blotting. Contractile responses of mesenteric arteries to α1-adrenoceptor agonist methoxamine as well as influences of NO and Rho-kinase did not differ between control and IUGR rats. However, coronary arteries of IUGR rats demonstrated elevated contraction to thromboxane A2 receptor agonist U46619 due to weakened anticontractile influence of NO and enhanced role of Rho-kinase in the endothelium. This was accompanied by reduced abundance of SODI protein and elevated content of RhoA protein in coronary arteries of IUGR rats. IUGR considerably changes the regulation of coronary vascular tone in adulthood and, therefore, can serve as a risk factor for the development of cardiac disorders.

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

Cited by 9 publications

References 43 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

Thyroxine Induces Acute Relaxation of Rat Skeletal Muscle Arteries via Integrin αvβ3, ERK1/2 and Integrin-Linked Kinase

Intrauterine growth restriction weakens anticontractile influence of NO in coronary arteries of adult rats

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

Cited by 9 publications

References 43 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

Thyroxine Induces Acute Relaxation of Rat Skeletal Muscle Arteries via Integrin αvβ3, ERK1/2 and Integrin-Linked Kinase

Intrauterine﻿ growth restriction weakens anticontractile influence of NO in coronary arteries of adult rats

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Intrauterine growth restriction weakens anticontractile influence of NO in coronary arteries of adult rats