Regulation of the Phenylethanolamine N‐methyltransferase Gene in the Spontaneous Hypertensive Rat

Phenylethanolamine N‐methyltransferase (PNMT) is the enzyme involved in the biosynthesis of the catecholamine, epinephrine. Genetic mapping studies suggest that the PNMT gene is a candidate gene for hypertension. Furthermore, elevated expression of PNMT is correlated with elevated blood pressure in hypertensive rats. However, the mechanism associated with changes in PNMT gene expression is not known. Recent studies have identified key transcriptional regulators of the PNMT gene, which include: Egr‐1, Sp1 and GR. The current study examined the mechanism by which dysregulation of the PNMT gene occurs in a genetic rodent model of hypertension. Results from the current study show that spontaneous hypertensive rats (SHR) have elevated systolic, diastolic and mean arterial blood pressure compared to Wistar‐Kyoto (WKY) rats at 14, 15 and 16 weeks of age. RT‐PCR analysis show that adrenal PNMT mRNA is 1.5‐fold higher in SHR compared to WKY, and have increased levels of transcription factors Egr‐1 (3.2‐fold), Sp1 (3.3‐fold) and GR (1.3‐fold). These results suggest that altered transcriptional activity may be involved in increased PNMT expression associated in the pathophysiology of hypertension.