Role of presympathetic C1 neurons in the sympatholytic and hypotensive effects of clonidine in rats

Schreihofer AM, Guyenet PG.
Am J Physiol Regul Integr Comp Physiol. 2000 Nov;279(5):R1753-62

   Clonidine is an a2-adrenergic receptor agonist that works in multiple places in the CNS. It is frequently used as an antihypertensive drug for its ability to decrease blood pressure. Microinjections of clonidine into the RVLM produce a drop in MAP, similar to IV administration, and the effect can be blocked by co-injection with an a2 antagonist. Earlier work had shown that slow firing (likely C1) neurons in the RVLM were affected by clonidine injection, but it wasn't clear if it was a direct effect on C1 neurons or if it was mediated by receptors on presynaptic cells. Also, the effect of clonidine on non-C1 presympathetic neurons was similarly unclear.
   To investigate these questions, RVLM neurons were recorded in rats that were treated with multiple IV doses of clonidine. Cells were also labeled with biotinamide for later reconstruction and examination of phenotype. They also used anti-DBH-saporin in some rats to lesion C1 cells to see what effect clonidine would have when the majority of C1 neurons had been eliminiated.
   They found that increasing doses of clonidine contributed to a gradually decreasing frequency of action potential frequency among all cell types - slow conducting (unmyelinated C1), medium conducting (mostly lightly myelinated C1) and fast conducting (mostly non-C1). They pointed out that the response was extremely variable within each group, and that overall SNA was more inhibited than any group was. So either something else which contributes to SNA was also inhibited, or that the nerve itself was inhibited somehow.
   After they reduced PNMT positive neurons in the rostral end of the C1 region by ~76% using anti-DBH-sapporin, they saw the same effect of clonidine as they did in untreated control and IgG-saporin control rats. So in this paper they showed that even though C1 neurons are inhibited by systemic clonidine and the inhibition could contribute to a decrease in SNA, C1 neurons aren't NECESSARY for this to happen, and that other non-C1 presympathetic neurons act the same way. - DH