Effects of locally administered desipramine on myocardial interstitial norepinephrine levels

We investigated whether locally administered neuronal uptake blockade with desipramine (DMI) modified basal myocardial interstitial norepinephrine (NE) levels and stimulation-induced NE responses. Using the dialysis technique, dialysates were sampled from the midwall of the left ventricle in anesthetized cats. Dialysate NE concentrations, as an index of myocardial interstitial NE level, were measured by high performance liquid chromatography. Through the dialysis probe, local administration of DMI (10(-4) mol/l) increased the dialysate NE level from 24.6 +/- 12.2 to 127.8 +/- 37.4 and from 11.9 +/- 5.4 to 64.9 +/- 28.7 pg/ml regardless of whether stellate ganglia were intact or transected. The arterial pressure and heart rate responses to electrical stimulation of the stellate ganglia were not altered by DMI. Control nerve stimulation increased dialysate NE concentrations to 214.5 +/- 100.0 and 57.5 +/- 22.0 pg/ml at 5 Hz and 2 Hz, respectively. During local administration of DMI, nerve stimulation-induced NE response increased to 997.5 +/- 202.0 at 5 Hz and to 436.0 +/- 68.5 pg/ml at 2 Hz. We conclude that local administration of DMI caused marked rises in basal myocardial interstitial NE concentrations and responses to cardiac sympathetic activation.