Adenosine Inhibits Exocytotic Release of Endogenous Noradrenaline in Rat Heart: A Protective Mechanism in Early Myocardial Ischemia
作者:
Gert Richardt,
Wolfgang Waas,
Roger Kranzhöfer,
Eckart Mayer,
Albert Schömig,
期刊:
Circulation Research
(OVID Available online 1987)
卷期:
Volume 61,
issue 1
页码: 117-123
ISSN:0009-7330
年代: 1987
出版商: OVID
数据来源: OVID
摘要:
&NA;The effects of exogenous and endogenous adenosine on exocytotic noradrenaline release were studied in rat hearts perfused in situ. Exocytotic release of endogenous noradrenaline (determined by high pressure liquid chromatography) was induced by electrical stimulation of the left cervicothoracic ganglion. Exogenous adenosine significantly reduced noradrenaline overflow from the heart. This suppression of noradrenaline overflow was not influenced by desipramine, indicating a mechanism independent from noradrenaline reuptake. The A1subtype specific agonists cyclohexyladenosine and R‐phenylisopropyladenosine had inhibitory effects at lower concentrations than adenosine and S‐phenylisopropyladenosine, suggesting the relevance of presynaptic inhibitory adenosine receptors of the A1subtype. Short ischemic periods of 3 minutes resulted in a marked coronary venous overflow of adenosine during reperfusion. This was accompanied by an inhibition of noradrenaline release evoked by nerve stimulation during ischemia. The adenosine antagonists theophylline and 8‐phenyltheophyl‐line prevented this suppression of noradrenaline release. Blockade of oxidative phosphorylation by cyanide in combination with glucose‐free perfusion induced an increased formation of endogenous adenosine and suppression of stimulation‐evoked noradrenaline overflow. Again, in the presence of the adenosine antagonists theophylline or 8‐phenyltheophylline, this suppression was abolished. These results indicate that adenosine is a potent inhibitor of exocytotic noradrenaline release in the heart with relevance during conditions of increased endogenous adenosine formation such as myocardial ischemia. (Circulation Research1987;61:117‐123)
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