Regulation of Sympathetic Tone and Arterial Pressure by the Rostral Ventrolateral Medulla after Depletion of C1 Cells in Rats
This review describes experiments designed to determine the role of bulbospinal (BS) C1 cells in regulating the sympathetic outflow and blood pressure. This goal was achieved by analyzing the physiological consequences of destroying BS C1 cells. These cells were destroyed by suicide transport of an anti-dopamine-beta-hydroxylase antibody conjugated to saporin (anti-D?H-SAP). Two to 3 weeks after spinal cord injection (T2-T6), the toxin destroyed 7585% of BS C1 and C3 cells along with >95% of BS noradrenergic neurons (A5, A6, A7). The toxin spared BS noncatecholaminergic cells. Under anesthesia, toxin-treated rats had a normal blood pressure and an apparently normal sympathetic nerve discharge (SNA, splanchnic), and intravenous clonidine caused a normal degree of sympathoinhibition. Inhibition of rostral ventrolateral medulla (RVLM) neurons by bilateral injection of muscimol caused the same hypotension and sympathoinhibition as in control rats. The baroreflex range was 41% attenuated by the toxin, but the MAP50 was unchanged. Sympathoexcitatory responses to stimulation of peripheral chemoreceptors with cyanide or to electrical stimulation of RVLM were severely depressed (60% to 80%) in toxin-treated rats. Rats in which A5 neurons were selectively destroyed had no deficit in the parameters tested. Unit recordings of BS RVLM neurons indicated that the toxin destroyed most barosensitive C1 neurons, but spared noncatecholaminergic lightly myelinated BS cells. In summary, the integrity of C1 neurons is not essential for the generation of SNA and the maintenance of BP under resting conditions, perhaps because these functions are performed primarily by noncatecholaminergic BS neurons. However, the deficits caused by treatment with anti-D?H-SAP indicate that BS C1 neurons play a crucial role in several sympathoexcitatory responses mediated by the RVLM.
saporin dopamine-beta-hydroxylase splanchnic nerve