Cortical catecholamine secretion following intravenous nitroprusside infusion: a voltammetric study

Intravenous administration of sodium nitroprusside (NP) decreases blood pressure and activates noradrenergic neurons in the locus coeruleus (LC). Microdialysis studies have shown that NP infusion is accompanied by increased extracellular concentrations of norepinephrine (NE) in the medial prefrontal cortex. The present study used in vivo voltammetry to obtain a finer temporal analysis of the NP-induced changes in the extracellular concentrations of catecholamine-like compounds in the LC terminal fields in the rat medial prefrontal cortex. Intravenous infusion of rats with NP caused a rapid decrease in blood pressure that lasted for the duration of the infusion but rapidly reversed when the infusion was terminated. After a delay of between about 2 and 8 min (mean 5 min), there was an increase in extracellular concentrations of a NE-like substance. Presumed cortical release of NE lasted for several minutes but had almost returned to baseline by the time the NP infusion was terminated at 15 min. In many cases, the first peak was followed by a second one, usually of smaller amplitude but more prolonged than the first one. There was no clear response to the cessation of infusion of NP. The time course of the initial response is comparable to the previously reported electrophysiological response of LC-NE neurons to NP. In rats treated with DSP-4 to deplete cortical NE, blood pressure was reduced as in untreated rats, but no voltammetric response to NP infusion was observed. These results suggest that activation of the NE-LC neurons by NP results in a delayed synaptic release of NE in the cerebral cortex which attenuates within several minutes.