Grant: Operating Grant

Hypertension or high blood pressure afflicts 1 in 4 adults in Canada and is the major contributing factor for cardiovascular disease, stroke and kidney disease. Currently, the underlying cause of 90-95% of all cases of hypertension is not known. Thus, understanding the potential risk factors and mechanisms involved in hypertension is critical to the development of novel treatments for this disease. Recent studies suggest that early-life environmental factors which influence fetal development may cause adult diseases such as hypertension. Although elevated prenatal levels of the stress hormone, glucocorticoids, are involved in programming of adult hypertension, the precise mechanism(s) are poorly understood. Due to the importance of the sympathetic nervous system, and the role of the adrenergic system in the development and maintenance of hypertension, we hypothesize that fetal programming of adult hypertension by involves permanent changes in adrenergic function involved in cardiovascular regulation. Thus, the studies proposed are designed to determine how changes in the adrenergic system during prenatal and early postnatal life contribute to the development of hypertension. Specifically, a focus on the role of the PNMT gene in fetal programming of hypertension will be delineated. This study will identify the period in postnatal life that is critical in programming of adult hypertension and the potential for preventing the development of hypertension with the use of PNMT inhibitors. In addition, this study will identify key cellular and molecular mechanisms that are involved in programming of adult hypertension via the PNMT gene. Ultimately, improving our understanding of fetal programming of adult hypertension can lead to the development of additional molecular targets that may be useful in the primary prevention of adult hypertension and thereby decrease the morbidity and mortality associated with this prevalent disease.