Sex differences in the fetal programming of hypertension: role of adrenal phenylethanolamine N‐methyltransferase gene expression (680.21)

Abstract

Prenatal exposure to high levels of glucocorticoids (GCs) predisposes to hypertension in later life. GCs regulate catecholamine biosynthesis and are critical for blood pressure homeostasis. This study examined whether prenatal exposure to elevated GCs influences the development of adult hypertension via alterations in phenylethanolamine N‐methyl transferase (PNMT), a gene that is linked to hypertension. Pregnant Wistar‐Kyoto dams were injected with 100 μg/kg/day of the synthetic GC dexamethasone (DEX) in their third trimester. Blood pressure and weights of the offspring were measured from week 3‐18, at which point the animals were sacrificed. Total RNA and protein were extracted from the adrenals, and the expression of PNMT and its regulatory transcription factors analyzed by qPCR and Western blot. Results reveal that in utero exposure to DEX promotes the development of hypertension in the offspring. A more pronounced increase in blood pressure was seen in males than females. The mRNA transcripts for PNMT, and its transcriptional regulators Egr‐1, Sp1, GR and AP‐2, were elevated in the adrenals of these animals compared to saline controls, with differences in both sexes. Preliminary Western data also shows upregulation of PNMT and the transcription factor Egr‐1. These results suggest that prenatal GC exposure increases adrenal PNMT gene expression via altered transcriptional regulatory mechanisms.Grant Funding Source: Supported by CIHR