Introduction: Developmental origins of disease refers to the theory that adverse maternal environments influence fetal development and the risk of cardiovascular disease (CVD) in adulthood. To test the hypothesis that gestational hypertension influences the development of CVD in offspring, a novel experimental paradigm was developed using atrial natriuretic peptide gene disrupted mice (ANP-/-). The objective of this thesis was to determine the effect of gestational hypertension on cardio-renal function in offspring. Methods: ANP+/+ females were crossed with ANP-/- males (yielding ANP+/-WT offspring) and ANP-/- females with ANP+/+ males (yielding ANP+/-KO offspring). Previous work has established that ANP-/- dams are hypertensive during pregnancy. Offspring gene expression was measured using qPCR. Offspring arterial blood pressure (BP) was measured with a non-invasive tail cuff system. Offspring left ventricular (LV) function was examined using echocardiography (ECHO). Offspring were treated with normal salt (NS) or high salt (HS) chow for five weeks to assess salt-sensitivity. Daily injections of isoproterenol (ISO) were used to induce cardiac stress in offspring. Collagen deposition was assessed using Masson’s trichrome and picrosirius red staining. Results: Absence of maternal ANP had no effect on either litter size or offspring growth, but caused significant LV hypertrophy in offspring, with no change in LV function. Treatment with ISO resulted in myocardial fibrosis and significant LV diastolic dysfunction with a restrictive filling pattern (increased E/A ratio and E/e’) only in ANP+/-KO offspring. Furthermore, absence of maternal ANP was associated with salt-resistant BP in offspring. Conclusions: Gestational hypertension using the ANP-/- mouse model results in a salt-resistant phenotype in offspring, as well as significant cardiac hypertrophy and an adverse response to activation of the sympathetic nervous system in adult offspring. These data suggest that adverse maternal environments may increase the risk of cardiovascular disease in offspring later in life. / Thesis (Ph.D, Anatomy & Cell Biology) -- Queen's University, 2012-09-18 16:12:01.147
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OKQ.1974/7559 |
| Date | 01 October 2012 |
| Creators | ARMSTRONG, DAVID |
| Contributors | Queen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.)) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner. |
| Relation | Canadian theses |
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