Characterization of Brainstem Phenylethanolamine N‐methyltransferase Gene Expression in Fetal Programming of Hypertension

Abstract

An unfavourable fetal environment results in low birth weight offsprings and the development of hypertension later in life. This concept of fetal programming proposes that elevated levels of glucocorticoids during fetal development leads to alterations in blood pressure regulatory mechanisms. Adrenaline, a neurotransmitter synthesized by the enzyme phenylethanolamine N‐methyltransferase (PNMT), is involved in the sympathetic control of blood pressure and is elevated in hypertensive patients. Dysregulation of the PNMT gene has been linked to the pathogenesis of hypertension and is therefore a candidate gene involved in fetal programming of hypertension. Results from this study show that Wistar Kyoto rats exposed to dexamethasone (DEX: 10, 50 or 100 μg/kg/day) in the third trimester, developed elevated blood pressure as adults. The elevations in arterial blood pressures correlate with the increased dose of prenatal DEX exposure. In addition, PNMT mRNA in the C1, C2 and C3 adrenergic brainstem regions were elevated in prenatally DEX exposed adult rats. Analysis of transcriptional regulators of the PNMT gene shows a dose‐dependent upregulation in the mRNA for Sp1, EGR‐1 and AP2 in the C2 and C3 regions; whereas GR mRNA was increased in the C3 region only. These results suggest that prenatal glucocorticoid exposure increases brainstem PNMT gene expression via altered transcriptional regulatory mechanisms.