Prenatal exposure to glucocorticoids (GCs) programs for hypertension later in life. The aim of the current study was to examine the impact of prenatal GC exposure on the postnatal regulation of the gene encoding for phenylethanolamine N-methyltransferase (PNMT), the enzyme involved in the biosynthesis of the catecholamine, epinephrine. PNMT has been linked to hypertension and is elevated in animal models of hypertension. Male offspring of Wistar-Kyoto dams treated with dexamethasone (DEX) developed elevated systolic, diastolic and mean arterial blood pressure compared to saline-treated controls. Plasma epinephrine levels were also elevated in adult rats exposed to DEX in utero. RT-PCR analysis revealed adrenal PNMT mRNA was higher in DEX exposed adult rats. This was associated with increased mRNA levels of transcriptional regulators of the PNMT gene: Egr-1, AP-2, and GR. Western blot analyses showed increased expression of PNMT protein, along with increased Egr-1 and GR in adult rats exposed to DEX in utero. Furthermore, gel mobility shift assays showed increased binding of Egr-1 and GR to DNA. These results suggest that increased PNMT gene expression via altered transcriptional activity is a possible mechanism by which prenatal exposure to elevated levels of GCs may program for hypertension later in life.

Biochemical changes in utero may alter normal fetal development, resulting in disease later in life, a phenomenon known as fetal programming. Recent epidemiological studies link fetal programming to negative health outcomes, such as low birth weight and hypertension in adulthood. Here, we used a WKY rat model and studied the molecular changes triggered by prenatal glucocorticoid (GC) exposure on the development of hypertension, and on the regulation of phenylethanolamine N-methyl transferase (PNMT), the enzyme responsible for biosynthesis of epinephrine, and a candidate gene linked to hypertension. Clinically, high doses of the synthetic GC dexamethasone (DEX) are used to treat infant respiratory distress syndrome. Elevated maternal GCs have been correlated with fetal programming of hypertension. The aim of this study was to determine if lower doses of DEX would not lead to detrimental fetal programming effects such as hypertension. Our data suggests that prenatal stress programs for increased expression of PNMT and altered regulation of PNMT in males and females. Importantly, we identified that DEX mediated programming was more apparent in the male rats, and the lower dose 10μg/kg/day of DEX did not lead to changes in blood pressure (BP) in female rats suggesting that this dose is below the threshold for programming of hypertension. Furthermore, sex-specific differences were observed in regards to programming mechanisms that may account for hypertension in males.

Fruit extracts of Dithyrea wislizenii were analyzed for desulfoglucosinolates and intact glucosinolates using HPLC-APCI-MS and HPLC-ESI-MS, respectively. 2-Propenylglucosinolate (sinigrin) was shown to be present in the extracts. 6-Methylsulfanylhexyl- (glucolesquerellin 9), 6-methylsulfinylhexyl- (glucohesperin 10), 7-methylsulfanylheptyl- (11), and 5-methylsulfanylpentylglucosinolate (glucoberteroin 12) were isolated from the extracts and characterized by NMR and MS data. 7-Methoxyglucobrassicin was not detected in D. wislizenii extracts.