Leptin-induced increase in blood pressure and markers of endothelial activation during pregnancy in Sprague Dawley rats is prevented by resibufogenin,a marinobufagenin antagonist |
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| Institution: | 1. Faculty of Medicine, Universiti Teknologi MARA Sungai Buloh Campus, Selangor, Malaysia;2. I-PPerFORM, Universiti Teknologi MARA, Malaysia;1. Departamento de Ciências Naturais, Universidade Federal de São João del Rei. Praça Dom Helvécio, 74 - Dom Bosco, São João del-Rei, MG, 36301-160, Brazil;2. Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, Belo Horizonte, MG, 31270-901, Brazil;3. Departamento de Zootecnia, ESALQ/Universidade de São Paulo, Av. Pádua Dias 11, Piracicaba, SP, 13418-900, Brazil;4. Embrapa Recursos Geneticos e Biotecnologia, PqEB, Av. W5 Norte, Brasília, DF, 70770-917, Brazil;1. Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;2. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;1. Department of Reproductive Center, First Affiliated Hospital ofGuangxi Medical University, Nanning, Guangxi, 530021, China;2. Department of Obstetrics and Gynecology, the Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, China;3. Reproductive Medicine Center, Liuzhou Maternal and Child Healthcare Hospital, Liuzhou, Guangxi, 545005, China;1. Human Cytogenetics, National Research Center, 12622, Cairo, Egypt;2. Department of Zoology, Faculty of Science, Minia University, 61519, El Minia, Egypt;3. Department of Clinical Genetics, National Research Center, 12622, Cairo, Egypt;1. Department of Physiology. University of the Basque Country (UPV/EHU), Leioa, Spain;2. Department of Biochemistry and Molecular Biology. University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain;3. Department of Biochemistry and Molecular Biology. University of Southern Denmark. Odense. Denmark;4. Center for Reproductive Medicine and Infertility Quirón Bilbao, Bilbao, Spain;1. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran;2. Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran;3. Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran;4. Industrial Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran;5. Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran;6. Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran |
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| Abstract: | Levels of leptin and marinobufagenin (MBG), a cardiotonic steroid, are elevated in the serum of women with pre-eclampsia. Besides this, leptin administration to pregnant rats increases systolic blood pressure (SBP), urinary protein excretion and serum markers of endothelial activation. The link between leptin and MBG is unknown and it is also unclear if leptin-induced increases in blood pressure and proteinuria in the pregnant rat could be prevented by an MBG antagonist. To ascertain this link, this study investigated the effect of resibufogenin (RBG), a marinobufagenin antagonist, on leptin-induced increases in blood pressure and proteinuria during pregnancy in rats.Four groups of Sprague-Dawley rats, aged 12 weeks, were given either normal saline (CONTROL) or 120 μg/kg/day of leptin (LEP), or 120 μg/kg/day of leptin+30 μg/kg/day of resibufogenin (L + RBG) or 30 μg/kg/day of resibufogenin (RBG) from Day 1–20 of pregnancy. Systolic blood pressure and urinary protein excretion (UPE) were measured during the study period. Animals were euthanized on day 21 of pregnancy and vascular cell adhesion molecule 1, (VCAM-1), soluble intracellular cell adhesion molecule 1 (sICAM-1), E-selectin and endothelin-1 (ET-1) were estimated in the serum.SBP, UPE, VCAM-1, sICAM-1 and ET-1 were significantly higher only in the LEP group when compared with those in CONT and in L + RBG and RBG groups.The prevention by RBG of leptin-induced increases in SBP, proteinuria, and endothelial activation during pregnancy seem to suggest a potential role for MBG in leptin-induced adverse effects on blood pressure, urinary protein excretion and endothelial activity during pregnancy in the rat. |
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| Keywords: | Leptin Blood pressure RBG Pregnancy Endothelial activation |
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