Metabolic modulation of cardiac neurosympathetic activity in vivo: effects of potassium and adenosine.
The effects of intracoronary (LAD) infusion of potassium and adenosine on changes in coronary vascular resistance and regional cardiac noradrenaline overflow during graded cardiac sympathetic stimulation were assessed in non-ischaemic myocardium in the open chest anaesthetised dog. Intracoronary potassium at three concentration (10, 25, 75 mmol.litre-1) progressively increased the potassium content of local venous effluent from 3.6 to 9.4 mmol.litre-1 and produced biphasic effects on nerve stimulated regional noradrenaline overflow. At low dose it was inhibitory (peak overflow at 20 Hz stimulation being reduced from (mean(SEM)) 10.2(2.6) to 2.9(1.8) pmol.ml-1 with 10 mmol.litre-1 potassium chloride; p less than 0.01). At high dose, overflow was potentiated to 13.3(2.7) pmol.ml-1 with 75 mmol.litre-1 potassium chloride (p less than 0.05). Noradrenaline overflow from and the potassium content of circumflex territory venous effluent was unchanged. Intracoronary adenosine at high concentration (10(-3) and 10(-2) mol.litre-1) potentiated basal noradrenaline overflow from the heart producing a small negative arteriovenous concentration difference of 0.6(0.7) and 1.0(0.6) pmol.ml-1 respectively. However, noradrenaline overflow during maximal sympathetic stimulation was inhibited from 3.8(1.4) to 0.4(0.7) pmol.ml-1 with 10(-3) mol.litre-1 adenosine and to 0.7(0.6) pmol.ml-1 with 10(-2) mol.litre-1 adenosine (p less than 0.05). The changes in blood flow and coronary vascular resistance seen with sympathetic stimulation were not modified by adenosine, despite major alteration in basal coronary vascular tone. Thus both metabolites may potentially alter local neurosympathetic activity in ischaemic myocardium and act diversely to determine noradrenaline release at the nerve terminal.
Forfar
J C
JC
Cardiovascular Research Unit, University of Edinburgh.
Riemersma
R A
RA
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006321:Heart / Q000294:innervation*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects
D000241:Adenosine; D011188:Potassium; D009638:Norepinephrine