Research articlePhenylethanolamine N-methyltransferase gene expression in adrenergic neurons of spontaneously hypertensive rats

- PNMT expression is increased in brainstem adrenergic regions of hypertensive rats.
- Characterization of transcriptional regulators of the PNMT gene.
- Egr-1 is significantly increased brainstem adrenergic regions.
- Altered transcriptional regulation of the brainstem PNMT gene may contribute to the pathogenesis of hypertension.

Epinephrine is synthesised by the catecholamine biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT), primarily in chromaffin cells of the adrenal medulla and secondarily in brainstem adrenergic neurons of the medulla oblongata. Epinephrine is an important neurotransmitter/neurohormone involved in cardiovascular regulation; however, overproduction is detrimental with negative outcomes such as cellular damage, cardiovascular dysfunction, and hypertension. Genetic mapping studies have linked elevated expression of PNMT to hypertension. Adrenergic neurons are responsible for blood pressure regulation and are the only PNMT containing neurons in the brainstem. The purpose of the current study was to determine whether elevated blood pressure found in adult spontaneously hypertensive rats (SHR) is associated with altered regulation of the PNMT gene in catecholaminergic neurons. C1, C2, and C3 adrenergic regions of 16 week old Wistar Kyoto (WKY) and SHR rats were excised using micropunch microdissection for mRNA expression analyses. Results from the current study confirm high PNMT mRNA expression in all three brainstem adrenergic regions (C1: 2.96-fold; C2: 2.17-fold; C3 1.20-fold) of the SHR compared to normotensive WKY rats. Furthermore, the immediate early gene transcription factor (Egr-1) mRNA was elevated in the C1 (1.84-fold), C2 (8.57-fold) and C3 (2.41-fold) regions in the brainstem of the SHR. Low mRNA expression for transcription factors Sp1 and GR was observed, while no change was observed for AP-2. The findings presented propose that alterations in the PNMT gene regulation in the brainstem contribute to enhanced PNMT production and epinephrine synthesis in the SHR, a genetic model of hypertension.