Effect of desipramine and cocaine on plasma norepinephrine and pressor responses to adrenergic stimulation in pithed rats.
Sympathetic neuronally released norepinephrine appears to act at intrajunctional alpha 1-adrenoceptors, whereas administered norepinephrine acts mostly at extrajunctional alpha 2-adrenoceptors. We examined the effects of inhibition of neuronal uptake of norepinephrine by desipramine (0.3 mg/kg iv) and cocaine (5 mg/kg iv) on the pressor effects and on plasma norepinephrine levels in pithed rats after the administration of norepinephrine (0.1, 0.3, and 1.0 micrograms/kg iv) or during stimulation of sympathetic outflow (0.1, 0.3, and 1.0 Hz at 50 V for 1 minute). Desipramine and cocaine potentiated the cardiovascular effects of administered norepinephrine to a greater extent than they potentiated the effects of sympathetic stimulation. Plasma levels of norepinephrine during sympathetic stimulation or after iv administration of norepinephrine were increased significantly after either desipramine or cocaine. The cardiovascular effects of sympathetic stimulation, but not of exogenous norepinephrine, were reduced in adrenomedullectomized rats compared to intact rats. In adrenomedullectomized rats, desipramine potentiates the pressor responses and enhances the increase in plasma norepinephrine levels during sympathetic stimulation to the same extent as in intact pithed rats. The preferential potentiation of administered norepinephrine by uptake inhibition is most likely due to enhancement of accessibility of circulating norepinephrine to otherwise inaccessible intrajunctional alpha 1-adrenoceptors. The higher concentrations of norepinephrine in the region of the nerve-ending limit release of the neurotransmitter by feedback inhibition via presynaptic alpha 2-adrenoceptors, thereby masking potentiation by uptake inhibition of the postsynaptic responses to sympathetic stimulation.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology*; D004298:Dopamine / Q000097:blood; D004558:Electric Stimulation; D004837:Epinephrine / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects*
D003042:Cocaine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine