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Regulation of the cardiac phenylethanolamine N‐methyltransferase gene in the spontaneously hypertensive rat
Author(s) -
Peltsch Heather,
Bizier C.,
Nguyen P.,
Wit J.,
Crispo J.,
Eibl J.,
Tai T.C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.776.5
Subject(s) - phenylethanolamine , phenylethanolamine n methyltransferase , epinephrine , medicine , endocrinology , downregulation and upregulation , messenger rna , gene expression , methyltransferase , catecholamine , biology , gene , chemistry , tyrosine hydroxylase , dopamine , genetics , methylation
Phenylethanolamine N‐methyltransferase (PNMT) is the terminal enzyme in the catecholamine biosynthetic pathway involved in the synthesis of epinephrine from norepinephrine. Recent studies have identified cardiac PNMT and endogenous epinephrine in the heart. Genetic mapping studies have linked the PNMT gene to hypertension, and elevated PNMT levels are associated with higher blood pressure in hypertensive rats. The current study examined the expression of the cardiac PNMT gene in the genetic rodent model of hypertension, and associated changes in transcriptional regulators of the gene. Results show upregulation of PNMT mRNA in all four chambers of the heart in spontaneously hypertensive rats (SHR) compared to Wistar‐Kyoto (WKY) rats, with the greatest fold change (2.18) in the right atrium (RA) (p<0.01). The transcription factors Egr‐1, Sp1 and GR have been previously identified as regulators of the PNMT promoter. RT‐PCR analyses show significant increases in Sp1 mRNA in all chambers of the heart of SHR. Further, Egr‐1 mRNA was upregulated in the right and left atria (1.90, 1.45 fold) in SHR. Western blots showed significant fold increases in Sp1 in SHR for the RA (1.74), and the left (2.72) and right (1.46) ventricles. Egr‐1 protein paralleled mRNA expression in SHR. These results show that PNMT gene expression is elevated in SHR, and is likely mediated by altered transcriptional regulation of PNMT in the heart.