Disposition of endogenous adrenaline compared to noradrenaline released by cardiac sympathetic nerves in the anaesthetized dog.
The fate of adrenaline released from cardiac sympathetic nerves was compared with that of noradrenaline before and during two periods of electrical stimulation of the left ansa subclavia in eight anaesthetized dogs. Cardiac spillovers and extractions of both catecholamines were estimated simultaneously using infusions of 3H-labelled adrenaline and noradrenaline. Animals were studied before and after neuronal uptake blockade with desipramine. Cardiac spillover of adrenaline, detectable at rest at 1.4 +/- 0.3 pmol/min, increased to 4.0 +/- 1.1 and 5.3 +/- 1.2 pmol/min during sympathetic stimulation. Cardiac noradrenaline spillover increased from 49 +/- 12 to 205 +/- 40 and 451 +/- 118 pmol/min. After desipramine, cardiac spillovers of adrenaline were decreased, whereas those of noradrenaline were increased so that the ratio of adrenaline to noradrenaline spillover, meaned before and during stimulation, decreased substantially from 1:42 to 1:166. The desipramine-induced decrease in cardiac extractions of 3H-labelled catecholamines indicated adrenaline was removed 60% less efficiently than noradrenaline by neuronal uptake, whereas the extractions remaining indicated adrenaline was removed 50% more efficiently by extraneuronal uptake. The differences in removal processes indicated that 35% of the adrenaline released by cardiac sympathetic nerves was recaptured compared to 88% for noradrenaline, leaving 53% to be removed extra-neuronally compared to 6.6% for noradrenaline, so that proportionally more released adrenaline than noradrenaline escaped to spillover into plasma (12% versus 5.4%). Since extra-neuronal uptake was more efficient for adrenaline than noradrenaline, proportionally less released adrenaline than noradrenaline escaped local removal to spillover into plasma when neuronal uptake was blocked (17% versus 45%). This reversed the situation before blockade so that desipramine substantially decreased the ratio of adrenaline to noradrenaline spillover. Thus, differences in the efficiencies of neuronal or extraneuronal uptake are important determinants of the amounts of locally released adrenaline and noradrenaline that escape removal processes to act at neuroeffector sites or spillover into plasma.
Eisenhofer
G
G
Baker Medical Research Institute, Prahran, Victoria, Australia.
Smolich
J J
JJ
Esler
M D
MD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D004837:Epinephrine / Q000378:metabolism*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008433:Mathematics; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*
D003891:Desipramine; D009638:Norepinephrine; D004837:Epinephrine