Summary
The aim of the study was to determine the sites of action of intravenously administered desipramine on the sympathetic nervous system in anaesthetized rabbits (alfadolone + alfaxalone). Renal postganglionic sympathetic nerve activity was measured in order to determine central nervous and ganglionic effects. The clearance of noradrenaline from the plasma was determined with an isotope tracer method. From the noradrenaline clearance and the plasma concentration of noradrenaline the noradrenaline spillover rate was calculated. These parameters as well as blood pressure and heart rate were measured before (basal values) and at the end of 20-min infusions of sodium nitroprusside, which was given in order to modulate efferent sympathetic nerve activity through the baroreceptors.
Desipramine 0.5 mg kg-1 + 0.05 mg kg−1 h−1 (bolus injection followed by infusion) and 2 mg kg−1 + 0.2 mg kg−1 h−1 dose-dependently inhibited basal sympathetic nerve activity and the noradrenaline clearance. Desipramine had no effect on basal blood pressure, noradrenaline spillover rate or heart rate. Nitroprusside produced hypotension and simultaneously increased sympathetic nerve activity, noradrenaline spillover rate and heart rate; the clearance of noradrenaline was reduced with decreasing blood pressure. The relationship between sympathetic nerve activity and blood pressure was shifted by desipramine in a manner indicating central sympathoinhibition. Desipramine had no effect on the relationship of the noradrenaline spillover rate to blood pressure, whereas it shifted the heart rate-blood pressure relationship in a manner indicating an enhancement of reflex cardioacceleration. In a separate series of experiments, desipramine also inhibited sympathetic nerve activity in baroreceptor-denervated animals.
The results show that desipramine centrally inhibits sympathetic outflow in the rabbit. Simultaneously, it enhances the noradrenaline spillover per action potential peripherally. In our study, the two effects compensated for each other, so that desipramine had no major effect on the relationship between noradrenaline spillover and blood pressure. In the heart, the peripheral effect of desipramine outweighed the central sympathoinhibition, hence the reflex cardioacceleration.
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Szabo, B., Schultheiss, A. Desipramine inhibits sympathetic nerve activity in the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 342, 469–476 (1990). https://doi.org/10.1007/BF00169466
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DOI: https://doi.org/10.1007/BF00169466