Evidence for a direct peripheral effect of clonidine on the norepinephrine release in vivo in pithed rats

To study the in vivo peripheral effects of clonidine on sympathetic neuronal function we measured, after different doses of clonidine, plasma norepinephrine (NE) and blood pressure (BP) responses during electric stimulation of sympathetic outflow in pithed male Sprague-Dawley rats. In this preparation, clonidine produced dose-dependent inhibition of the sympathetic stimulation-induced pressor and plasma NE responses. The dose of clonidine inhibiting the NE response by 50% (ID50) was 14.2 +/- 0.3 micrograms/kg i.v., while ID50 for the diastolic pressor response was 22.0 +/- 0.2 micrograms/kg i.v. Since clonidine did not alter the relationship between NE released into the plasma and the pressor responses, the entire effect of clonidine in decreasing the pressor response to sympathetic stimulation may be attributed to its presynaptic alpha 2-adrenoceptor-mediated inhibition of NE release.