Dina K Gaynullina1,2,3, Svetlana I Sofronova4,5, Anastasia A Shvetsova4,5, Ekaterina K Selivanova4,5, Anna P Sharova5, Andrey A Martyanov4,5, Olga S Tarasova4,5. 1. Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, Moscow, 119234, Russia. dina.gaynullina@gmail.com. 2. Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76 A, Moscow, 123007, Russia. dina.gaynullina@gmail.com. 3. Department of Physiology, Russian National Research Medical University, Ostrovitianova str. 1, 117997, Moscow, Russia. dina.gaynullina@gmail.com. 4. Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1/12, Moscow, 119234, Russia. 5. Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe shosse 76 A, Moscow, 123007, Russia.
Abstract
BACKGROUND: Maternal thyroid deficiency can increase Rho-kinase procontractile influence in arteries of 2-week-old progeny. Here we hypothesized that augmented role of Rho-kinase persists in arteries from adult progeny of hypothyroid rats. METHODS: Dams were treated with 6-propyl-2-thiouracil (PTU) in drinking water (0.0007%) during pregnancy and 2 weeks postpartum; control (CON) females received PTU-free water. At the age of 10-12-weeks, serum T3/T4 levels did not differ between PTU and CON male offspring. Cutaneous (saphenous), mesenteric, and skeletal muscle (sural) arteries were studied by wire myography, qPCR, and Western blotting. RESULTS: Saphenous arteries of PTU and CON groups showed similar responses to α1-adrenoceptor agonist methoxamine and were equally suppressed by Rho-kinase inhibitor Y27632. Responses of mesenteric arteries also did not differ between PTU and CON, but the effects of Y27632 were more prominent in the PTU group. Sural arteries of PTU rats compared to CON demonstrated augmented responses to methoxamine, increased RhoA mRNA contents and higher levels of MYPT1 phosphorylation at Thr855. Intergroup differences in contractile responses and phospho-MYPT1-Thr855 were eliminated by Y27632. CONCLUSION: Rho-kinase contribution to contractile responses of mesenteric and especially sural arteries is augmented in adult PTU rats. Therefore, maternal thyroid deficiency may have long-term detrimental consequences for vasculature in adult offspring.
BACKGROUND:Maternal thyroid deficiency can increase Rho-kinase procontractile influence in arteries of 2-week-old progeny. Here we hypothesized that augmented role of Rho-kinase persists in arteries from adult progeny of hypothyroidrats. METHODS: Dams were treated with 6-propyl-2-thiouracil (PTU) in drinking water (0.0007%) during pregnancy and 2 weeks postpartum; control (CON) females received PTU-free water. At the age of 10-12-weeks, serum T3/T4 levels did not differ between PTU and CON male offspring. Cutaneous (saphenous), mesenteric, and skeletal muscle (sural) arteries were studied by wire myography, qPCR, and Western blotting. RESULTS: Saphenous arteries of PTU and CON groups showed similar responses to α1-adrenoceptor agonist methoxamine and were equally suppressed by Rho-kinase inhibitor Y27632. Responses of mesenteric arteries also did not differ between PTU and CON, but the effects of Y27632 were more prominent in the PTU group. Sural arteries of PTUrats compared to CON demonstrated augmented responses to methoxamine, increased RhoA mRNA contents and higher levels of MYPT1 phosphorylation at Thr855. Intergroup differences in contractile responses and phospho-MYPT1-Thr855 were eliminated by Y27632. CONCLUSION: Rho-kinase contribution to contractile responses of mesenteric and especially sural arteries is augmented in adult PTUrats. Therefore, maternal thyroid deficiency may have long-term detrimental consequences for vasculature in adult offspring.
Authors: Dina K Gaynullina; Svetlana I Sofronova; Ekaterina K Selivanova; Anastasia A Shvetsova; Anna A Borzykh; Olga S Tarasova Journal: Curr Res Physiol Date: 2021-12-14
Authors: Ekaterina K Selivanova; Anastasia A Shvetsova; Lyubov D Shilova; Olga S Tarasova; Dina K Gaynullina Journal: Sci Rep Date: 2021-07-14 Impact factor: 4.379