Cardiac epinephrine synthesis and ischemia-induced myocardial epinephrine release.
OBJECTIVE
Phenylethanolamine-N-methyltransferase (PNMT), the enzyme that synthesizes epinephrine (EPI) from norepinephrine (NE) in the adrenal gland, is present in extra-adrenal tissues including heart. Ischemia evokes an excessive NE accumulation in the myocardial interstitial spaces. Therefore, cardiac PNMT activity with high NE levels may contribute to cardiac EPI synthesis and release evoked by ischemia.


METHODS
We measured dialysate EPI levels in the left ventricle of anesthetized rabbits using a cardiac microdialysis technique. The dialysate EPI level served as an index of the myocardial interstitial EPI level. Locally administered NE-induced dialysate EPI responses were measured. The left circumflex coronary artery was occluded for 60 min and the dialysate EPI and NE levels in the ischemic region were measured. Coronary occlusion-induced EPI responses were compared with and without administration of a PNMT inhibitor (SKF29661) in the presence and absence of desipramine (catecholamine transport blocker).


RESULTS
Local administration of NE (250, 2500 ng/ml) increased the EPI levels to 734+/-125 and 2088+/-367 pg/ml respectively. These increases in dialysate EPI were suppressed by the PNMT inhibitor. Acute myocardial ischemia significantly increased the EPI levels to 3607+/-1069 pg/ml in the ischemic region, and these were suppressed by the PNMT inhibitor (1417+/-581 pg/ml). The pretreatment with desipramine suppressed ischemia-induced EPI release, which did not differ with (725+/-155 pg/ml) and without administration of a PNMT inhibitor (743+/-172 pg/ml).


CONCLUSIONS
The cardiac PNMT in the left ventricle is capable of synthesizing EPI with markedly elevated NE levels in the myocardial interstitial space.
Kuroko
Yosuke
Y
Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, 700-8558, Japan.
Yamazaki
Toji
T
Tokunaga
Noriyuki
N
Akiyama
Tsuyoshi
T
Kitagawa
Hirotoshi
H
Ishino
Kozo
K
Sano
Shunji
S
Mori
Hidezo
H
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D003956:Dialysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000096:biosynthesis* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits
D018759:Adrenergic Uptake Inhibitors; D004791:Enzyme Inhibitors; D007546:Isoquinolines; C018428:1,2,3,4-tetrahydroisoquinoline-7-sulfonamide; D010625:Phenylethanolamine N-Methyltransferase; D003891:Desipramine; D004837:Epinephrine