Extraneuronal enzymatic degradation of myocardial interstitial norepinephrine in the ischemic region

Takafumi Fujii, Toji Yamazaki, Tsuyoshi Akiyama, Shunji Sano, Hidezo Mori

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)125-131
Number of pages7
JournalCardiovascular Research
Volume64
Issue number1
DOIs
Publication statusPublished - Oct 1 2004

Fingerprint

Catechol O-Methyltransferase
Norepinephrine
Ischemia
Coronary Occlusion
Myocardial Ischemia
Myocardium
Methoxyhydroxyphenylglycol
Normetanephrine
Dialysis Solutions
Monoamine Oxidase
Microdialysis
Reperfusion
dihydroxyphenylethylene glycol
Coronary Vessels
entacapone
Rabbits

Keywords

  • Adrenergic agonists
  • Autonomic nervous system
  • Ischemia
  • Neurotransmitters
  • Reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Extraneuronal enzymatic degradation of myocardial interstitial norepinephrine in the ischemic region. / Fujii, Takafumi; Yamazaki, Toji; Akiyama, Tsuyoshi; Sano, Shunji; Mori, Hidezo.

In: Cardiovascular Research, Vol. 64, No. 1, 01.10.2004, p. 125-131.

Research output: Contribution to journalArticle

Fujii, Takafumi ; Yamazaki, Toji ; Akiyama, Tsuyoshi ; Sano, Shunji ; Mori, Hidezo. / Extraneuronal enzymatic degradation of myocardial interstitial norepinephrine in the ischemic region. In: Cardiovascular Research. 2004 ; Vol. 64, No. 1. pp. 125-131.
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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.",
keywords = "Adrenergic agonists, Autonomic nervous system, Ischemia, Neurotransmitters, Reperfusion",
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T1 - Extraneuronal enzymatic degradation of myocardial interstitial norepinephrine in the ischemic region

AU - Fujii, Takafumi

AU - Yamazaki, Toji

AU - Akiyama, Tsuyoshi

AU - Sano, Shunji

AU - Mori, Hidezo

PY - 2004/10/1

Y1 - 2004/10/1

N2 - 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.

AB - 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.

KW - Adrenergic agonists

KW - Autonomic nervous system

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KW - Neurotransmitters

KW - Reperfusion

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