Grant: Travel Awards - Institute Community Support

Hypertension is a complex disease that affects 1 in 3 individuals world-wide and is influenced by a combination of genetic and environmental factors. Epidemiological evidence suggests that an insult on the fetal environment results in low birth weight offspring and is correlated with the development of hypertension later in life. This concept of fetal programming proposes that a suboptimal environment along with the production of stress hormones during fetal development leads to alterations in blood pressure regulatory mechanisms. Adrenaline is a neurotransmitter involved in the control of blood pressure and is elevated in hypertensive patients. It is converted from noradrenaline by the enzyme phenylethanolamine N-methyltransferase (PNMT). The dysregulation of the PNMT gene has been linked to the pathogenesis of hypertension and is therefore a candidate gene involved in the fetal programming of adult hypertension. Results from the current study demonstrate that Wistar Kyoto rats subjected to prenatal administration of dexamethasone (Dex 10, 50 or 100 ug/kg/day) in the third trimester experience elevated blood pressure and are significantly and positively correlated with the increased dose of prenatal Dex administration, in a dose dependent fashion. In addition, results from qRT-PCR show that PNMT mRNA is upregulated, also in a dose dependent manner, in the C1, C2 and C3 adrenergic brainstem regions of prenatally dexamethasone exposed adult rats, compared to the saline control group. Furthermore, transcriptional regulator levels of Sp1, EGR-1 and AP2 show elevations in mRNA expression in only C2 and C3 adrenergic neurons when rats are prenatally exposed to dexamethasone. The expression of GR mRNA was only increased in the C3 adrenergic brainstem region with dexamethasone exposure.Results from the current study suggest prenatal glucocorticoid exposure increases brainstem PNMT gene expression caused by altered transcriptional regulatory mechanisms.