当前位置： SCI文献检索 > CARDIOVASCULAR RESEARCH期刊下所有文献 > Extraneuronal enzymatic degradation of myocardial interstitial norepinephrine in the ischemic region.

Extraneuronal enzymatic degradation of myocardial interstitial norepinephrine in the ischemic region.

Abstract：

OBJECTIVE:Catechol O-methyltransferase (COMT) is believed to exert degradative action at high norepinephrine (NE) levels. Although COMT exists in cardiac tissues, the contribution of cardiac COMT activity to regional NE kinetics, particularly in ischemia-induced NE accumulation, remains unclear. We investigated the role of cardiac COMT in NE kinetics in the ischemic region. METHODS:We implanted a microdialysis probe into the left ventricular myocardium of anesthetized rabbits and induced myocardial ischemia by 60-min coronary artery occlusion. We monitored myocardial interstitial levels of NE and its metabolites in the presence and absence of a COMT inhibitor. We intraperitoneally administered entacapone (10 mg/kg) 120 min before control sampling. RESULTS:In control, entacapone increased interstitial dihydroxyphenylglycol (DHPG, intraneuronal NE metabolite by monoamine oxidase (MAO)) levels and decreased interstitial normetanephrine (NMN, extraneuronal NE metabolite by COMT) and 3-methoxy-4-hydroxyphenylglycol (MHPG, extraneuronal DHPG metabolite by COMT) levels, but did not change interstitial NE levels. Coronary occlusion increased NE levels to 165+/-48 nM at 45-60 min of occlusion. This increase was accompanied by increases in DHPG and NMN levels (11.3+/-1.1 and 9.3+/-1.3 nM at 45-60 min of occlusion). Entacapone augmented the ischemia-induced NE and DHPG responses (333+/-51 and 22.9+/-2.4 nM at 45-60 min of occlusion). In contrast, the ischemia-induced NMN response was suppressed by entacapone (2.0+/-0.4 nM at 45-60 min of occlusion). Reperfusion decreased interstitial NE levels and increased interstitial DHPG and NMN levels. Entacapone suppressed changes in NE and NMN levels, but augmented the increase in dialysate DHPG. CONCLUSION:Myocardial ischemia evoked increases in myocardial interstitial NE and NMN levels. COMT inhibition augmented the increase in NE (substrate of COMT) levels and suppressed the increase in NMN (metabolite by COMT) levels. In the ischemic heart, COMT contributes to the removal of accumulated NE in the myocardium.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Fujii T,Yamazaki T,Akiyama T,Sano S,Mori H

doi

10.1016/j.cardiores.2004.06.011

subject

Has Abstract

pub_date

2004-10-01 00:00:00

pages

125-31

issue

eissn

0008-6363

issn

1755-3245

pii

S0008636304002536

journal_volume

pub_type

杂志文章

在线工具

Extraneuronal enzymatic degradation of myocardial interstitial norepinephrine in the ischemic region.