Effect of sildenafil citrate treatment in the eNOS knockout mouse model of fetal growth restriction on long-term cardiometabolic outcomes in male offspring
| Autor: | Jasmine F. Plows, Mark H. Vickers, Huan Zhao, Charlotte Oyston, Valerie J. Mills, Joanna L. Stanley, Philip N. Baker |
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| Rok vydání: | 2017 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Nitric Oxide Synthase Type III Offspring Sildenafil Blood Pressure 030204 cardiovascular system & hematology Placebo Diet High-Fat Sildenafil Citrate 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Insulin resistance Pregnancy Internal medicine Medicine Weaning Animals Insulin Maternal-Fetal Exchange Adiposity Pharmacology Mice Knockout 030219 obstetrics & reproductive medicine Fetal Growth Retardation business.industry medicine.disease Mesenteric Arteries Mice Inbred C57BL Blood pressure Endocrinology chemistry Gestation Female business |
| Zdroj: | Pharmacological research. 137 |
| ISSN: | 1096-1186 |
| Popis: | Fetal growth restriction (FGR) is associated with an increased risk of hypertension, insulin resistance, obesity and cardiovascular disease in adulthood. Currently there are no effective treatments to reverse the course of FGR. This study used the eNOS knockout mouse (eNOS−/−), a model of FGR, to determine the ability of sildenafil, a potential new treatment for FGR, to improve cardiovascular and metabolic outcomes in adult offspring following a complicated pregnancy. Pregnant eNOS−/− and C57BL/6J control dams were randomised to sildenafil treatment (0.2 mg/ml in drinking water) or placebo at day 12.5 of gestation until birth. After weaning, male offspring were randomised to either a high fat (HFD; 45% kcal from fat) or normal chow diet (ND), and raised to either postnatal day 90 or 150. Growth and body composition, glucose tolerance, insulin resistance, systolic blood pressure and vascular function were analysed at both time-points. eNOS−/− offspring were significantly smaller than their C57BL/6J controls at weaning and P90 (p Both diet and maternal sildenafil treatment had a significant effect on glucose tolerance. Glucose tolerance was significantly impaired in eNOS−/− mice fed a HFD (p Exposure to sildenafil was associated with a significant increase in systolic blood pressure in eNOS−/− mice compared with their C57BL/6J diet controls at P150 (p eNOS−/− mice demonstrate a number of impaired outcomes consistent with programmed cardiometabolic disease, particularly when faced with the ‘second hit’ of a HFD. Exposure to sildenafil treatment during pregnancy did not increase fetal growth or significantly improve adult metabolic or cardiac outcomes. Maternal sildenafil treatment was, however, associated with small impairments in glucose handling and an increase in blood pressure. This study highlights the importance of understanding the long-term effects of treatment during pregnancy in offspring from both complicated and healthy control pregnancies. |
| Databáze: | OpenAIRE |
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