Abstract
Serotonin is thought to contribute to the syncopal-like response that develops during severe blood loss by inhibiting presympathetic neurons of the rostroventrolateral medulla (RVLM). Here, we tested whether serotonin cells activated during hypotensive hemorrhage, i.e., express the protein product of the immediate early gene c-Fos, are critical for the normal sympathetic response to blood loss in unanesthetized rats. Serotonin-immunoreactive cells of the raphe obscurus and raphe magnus, parapyramidal cells of the B3 region, subependymal cells of the ventral parapyramidal region, and cells of the ventrolateral periaqueductal gray region were activated by hypotensive hemorrhage, but not by hypotension alone. In contrast to findings in anesthetized animals, lesion of hindbrain serotonergic cells sufficient to produce >80% loss of serotonin nerve terminal immunoreactivity in the RVLM accelerated the sympatholytic response to blood loss, attenuated recovery of sympathetic activity after termination of hemorrhage, and exaggerated metabolic acidosis. Hindbrain serotonin lesion also attenuated ventilatory and sympathetic responses to stimulation of central chemoreceptors but increased spontaneous arterial baroreflex sensitivity and decreased blood pressure variability. A more global neurotoxic lesion that also eliminated tryptophan hydroxylase-immunoreactive cells of the ventrolateral periaqueductal gray region had no further effect on the sympatholytic response to blood loss. Together, the data indicate that serotonin cells of the caudal hindbrain contribute to compensatory responses following blood loss that help maintain oxygenation of peripheral tissue in the unanesthetized rat. This effect may be related to facilitation of chemoreflex responses to acidosis.