title: Reduced neuronal noradrenaline overflow in the ischaemic rat heart: importance of the severity of coronary flow reduction.
abstract: The effects of severity and duration of acute myocardial ischaemia on left stellate ganglion stimulation-induced noradrenaline (NA) overflow were studied in the retrogradely perfused, innervated rat heart. A 10-min period of ischaemia induced by a coronary flow reduction of 100% (0 ml/g/min), 95% (0.24 ml/g/min) and 90% (0.48 ml/g/min) reduced neuronal NA overflow to 24 +/- 4% (p less than 0.01), 62 +/- 6% (p less than 0.05) and 70 +/- 6% (p less than 0.05) of the normoxic control values, respectively. During low-flow ischaemia, a progressive decline in neuronal NA overflow was found in hearts subjected to 95% flow reduction, but not to 90% flow reduction. The effect of ischaemia on presynaptic control of NA release was also examined. After 10 min of stop-flow ischaemia, the alpha-adrenergic antagonist phentolamine (1 microM) and the adenosine receptor antagonist 8-phenyltheophylline (10 microM) failed to restore neuronal NA overflow to pre-ischaemic levels (from 24 +/- 4% without drug to 23 +/- 4% or 41 +/- 10%, respectively, NS). In contrast, after 60 min of low-flow ischaemia (95% flow reduction), phentolamine and 8-phenyltheophylline largely restored neuronal NA overflow to normoxic control values (from 32 +/- 3% without drug to 61 +/- 11% (p less than 0.05) or 79 +/- 11% (p less than 0.01), respectively). During prolonged low-flow ischaemia (95%), the neuronal NA reuptake inhibitor desipramine (0.1 microM) doubled NA overflow induced by nerve stimulation, suggesting an effective neuronal reuptake during these conditions. In conclusion, the severity of ischaemia critically affects neuronal NA release and its controlling mechanisms. Thus, heterogeneity of myocardial ischaemia may lead to gradients in NA release and myocardial adrenergic stimulation.
authors.affiliation: Department of Medicine (RIE), University of Edinburgh, United Kingdom.
authors.forename: X J
authors.initials: XJ
authors.lastname: Du
authors.forename: R A
authors.initials: RA
authors.lastname: Riemersma
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D004558:Electric Stimulation; D006863:Hydrogen-Ion Concentration; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D007773:Lactates / Q000032:analysis; D019344:Lactic Acid; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D058914:Purinergic Antagonists; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear; D011983:Receptors, Purinergic / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C037688:ADP-ATP carrier receptor; D007773:Lactates; D058914:Purinergic Antagonists; D011942:Receptors, Adrenergic, alpha; D018160:Receptors, Cytoplasmic and Nuclear; D011983:Receptors, Purinergic; D019344:Lactic Acid; D013806:Theophylline; C028322:8-phenyltheophylline; D007770:L-Lactate Dehydrogenase; D003891:Desipramine; D009638:Norepinephrine; D010646:Phentolamine