Cardiac epinephrine synthesis. Regulation by a glucocorticoid.
BACKGROUND
The heart can synthesize epinephrine. Homogenates of rat heart, which contain the enzymes phenylethanolamine N-methyltransferase (PNMT) and nonspecific N-methyltransferase (NMT), methylate norepinephrine to form epinephrine. The cardiac atrium contains primarily PNMT and the cardiac ventricle contains both PNMT and NMT.


RESULTS
Rats were given the glucocorticoid dexamethasone at doses ranging from 0.2 to 20 mg/kg. Twenty-four hours later, cardiac atria, ventricle, skeletal muscle, and adrenal had increases in PNMT activity to as much as 230% of baseline. NMT activity was unchanged. Longer-term treatment with 1 mg/kg dexamethasone daily for 12 days increased cardiac PNMT activity about fivefold and also increased atrial epinephrine levels. Dexamethasone did not alter ventricular epinephrine levels but increased levels of both PNMT and catechol-O-methyltransferase, the major catabolic enzyme for epinephrine. After dexamethasone treatment, greater volumes of anti-PNMT antiserum were needed to decrease PNMT enzymatic activity, indicating that dexamethasone treatment resulted in greater amounts of PNMT and did not just activate existing PNMT molecules. Denervation of the masseter muscle of rats by unilateral superior cervical ganglionectomy markedly diminished tissue norepinephrine and epinephrine levels but had no effect on masseter PNMT or NMT levels. We have previously shown that chemical sympathectomy with 6-hydroxydopamine increases cardiac PNMT levels. These findings suggest that PNMT is an extraneuronal enzyme in both cardiac and skeletal muscle.


CONCLUSIONS
Glucocorticoids have several cardiovascular effects, including increased cardiac output and blood pressure. Enhanced cardiac epinephrine synthesis may mediate some of these glucocorticoid effects.
Kennedy
B
B
Department of Medicine, University of California, San Diego Medical Center 92103.
Ziegler
M G
MG
D000313:Adrenal Medulla; D000315:Adrenalectomy / Q000379:methods; D000818:Animals; D003655:Decerebrate State; D003907:Dexamethasone / Q000494:pharmacology*; D004837:Epinephrine / Q000096:biosynthesis*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013562:Sympathectomy
D003907:Dexamethasone; D010625:Phenylethanolamine N-Methyltransferase; D004837:Epinephrine