Regulation of adrenaline synthesis in the heart of the spontaneously hypertensive rat

Abstract

Phenylethanolamine N‐methyltransferase (PNMT) is the enzyme responsible for adrenaline synthesis. Adrenaline is involved in sympathetic control of blood pressure, and it augments cardiac function. Genetic mapping studies have linked PNMT to hypertension, and elevated PNMT levels are associated with higher blood pressure in hypertensive rats. The current study examined the expression of cardiac PNMT in the genetic rodent model of hypertension, and associated changes in the transcriptional regulators. RT‐PCR results show upregulation of PNMT in all chambers of the heart of spontaneously hypertensive rats (SHR) compared to Wistar‐Kyoto (WKY). RT‐PCR analyses of the previously identified key regulators of PNMT, Egr‐1, Sp1, AP2 and GR, show significant increases in all chambers of the SHR heart. Protein levels of Sp1, Egr‐1 and GR are elevated in the right atrium (RA) of SHR. In addition, AP2 shows increased binding to its cognate promoter sequence in SHR hearts. Plasma levels of corticosterone and MCP‐1 are significantly elevated in SHR, while IL‐1‐beta, IL‐12p70, IL‐18 and IFN‐gamma are significantly lower in SHR compared to WKY. These results show elevated PNMT gene expression in SHR that is likely mediated by altered transcriptional regulation of cardiac PNMT. Furthermore, SHR display systemic differences from WKY in hypothalamic‐pituitary‐adrenal axis activity and cytokine profiles in circulation.