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To determine whether differential sympathetic nerve responses to hypoxia are explained by opposing effects of hypoxia upon sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM), the cardiac sympathetic nerve and the renal sympathetic nerve were recorded in anesthetized and vagotomized rabbits. Renal sympathetic nerve was activated by the injection of sodium cyanide solution close to the bifurcation of the common carotid artery and/or by inhalation of hypoxic gas (3% oxygen-97% nitrogen). On the other hand, cardiac sympathetic nerve was inhibited by these stimuli. Barosensitive (inhibited by the stimulation of baroreceptor afferents) reticulospinal (antidromically activated by the stimulation of the spinal cord) neurons in the RVLM were divided into three groups according to their responses to hypoxic stimulation: neurons (Type I, n = 25), the activity of which was inhibited by the injection of sodium cyanide solution close to the bifurcation of the common carotid artery and/or by inhalation of hypoxic gas, neurons (Type II, n = 99), the activity of which was facilitated by the same stimulation, and neurons (Type III, n = 11), the activity of which was not changed. These data indicated that the differential responses of cardiac and renal sympathetic nerves might be due to opposing effects of hypoxia on individual RVLM neurons.

The arterial baroreceptor-sympathetic vasoconstrictor reflex (baroreceptor reflex), among autonomic reflexes, is summarized. Arterial baroreceptor afferents terminate in the caudal part of the nucleus tractus solitarius. Excitation of the baroreceptor afferents activates neurons in the caudal ventrolateral medulla that send axonal projections to the rostral ventrolateral medulla. These neurons (CVLM neurons) then inhibit tonic activity of sympathoexcitatory reticulospinal neurons in the rostral ventrolateral medulla (RVLM neurons). Tonic activity of RVLM neurons are responsible for tonic activity of the peripheral vasoconstrictors. These two kinds of neurons are essential neuronal components for the baroreceptor reflex. Both the neurons may also participate in various vasoconstrictor reflexes, such as the somato-and viscero-sympathetic vasoconstrictor reflexes.

Participation of the caudal ventrolateral medulla in the arterial baroreceptor reflex was examined in urethane-anesthetized, vagotomized and immobilized rabbits whose aortic nerve was cut bilaterally. The extent of the caudal ventrolateral medulla was mapped by decreases in the renal sympathetic nerve activity and arterial pressure following a local microinjection of a neuroexcitatory amino acid, sodium glutamate (0.075-1.5 nmol). It extended between the levels 1.3 mm rostral and 3.0 mm caudal to the obex. An injection of sodium glutamate into the caudal ventrolateral medulla also diminished spontaneous activity of barosensitive reticulospinal neurons in the rostral ventrolateral medulla. In the 'split medulla preparation' in which the medulla was split along the midsagittal plane to disrupt fiber connections associating both sides, a neurotoxic agent, kainic acid, was injected unilaterally into the rostral ventrolateral medulla. This treatment markedly attenuated responses of renal sympathetic nerve activity and arterial pressure induced by a sodium glutamate injection into the ipsilateral caudal ventrolateral medulla, whereas responses to an injection into the contralateral caudal ventrolateral medulla were totally preserved. In four separate experiments, three to five injections of kainic acid were made unilaterally to cover the whole extent of the caudal ventrolateral medulla. The sympathoinhibitory and depressor responses to stimulation of the ipsilateral aortic nerve were then totally abolished. Simultaneously, the cardiac cycle-related rhythmic fluctuation of renal sympathetic nerve activity, which represented activity of the carotid sinus baroreceptor reflex, was attenuated to the noise level. These results, together with our previous electrophysiological demonstration of barosensitive caudal ventrolateral medulla neurons with axonal projections to the rostral ventrolateral medulla, strongly support the hypothesis that neurons in the caudal ventrolateral medulla mediate the arterial baroreceptor-vasomotor reflex through inhibition of barosensitive reticulospinal neurons in the rostral ventrolateral medulla.

In urethane-anesthetized rabbits, we successfully recorded unit activity of four neurons in the caudal ventrolateral medulla (CVLM) that were excited by orthodromic stimulation of the aortic nerve and by antidromic stimulation of the rostral ventrolateral medulla (RVLM). The sum of mean onset latency of excitation to stimulation of the aortic nerve (37.5 ms) and mean conduction time of antidromic spikes (10.5 ms) was close to the mean onset latency of inhibition of reticulospinal neurons in the RVLM to stimulation of the aortic nerve (47.1 ms) as previously reported by us. Three of 4 neurons received excitatory input from carotid sinus baroreceptors as well. Our results provide strong evidence for the hypothesis that neurons in the CVLM subserve the arterial baroreceptor-sympathetic vasomotor reflex.

In 55 anesthetized and paralyzed adult rabbits, 161 spontaneously active neurons which responded to electrical stimulation of A-fibers of the aortic nerve were found within the ventrolateral medulla (VLM). They were termed barosensory VLM neurons, since the aortic nerve A-fibers were considered to consist exclusively of afferents from arterial baroreceptors. Forty percent of barosensory VLM neurons tested (49/123) were activated antidromically by stimulation of the dorsolateral funiculus indicating that they send descending bulbospinal projections. Spontaneous discharges of barosensory VLM neurons were invariably inhibited by stimulation of aortic nerve A-fibers. Ninety-three percent of 80 neurons tested also responded to stimulation of aortic nerve C-fibers, a mixture of barosensory and nonbarosensory afferents. Natural stimulation of carotid sinus baroreceptors by an intravenous injection of phenylephrine in 19 vagotomized rabbits with aortic nerves disrupted inhibited spontaneous activity of all the 50 barosensory VLM neurons tested. By contrast, pharmacological stimulation of right or left carotid body chemoreceptors by close arterial injection of NaCN into the carotid sinus augmented activity of 93% of barosensory VLM neurons tested (41/44). The neuronal response was always greater to stimulation of chemoreceptors in the contralateral carotid sinus. Seven out of 8 barosensory VLM neurons tested (88%) were orthodromically excited by stimulation of the posterior hypothalamic area. In 74% of the 97 neurons examined in 29 vagotomized animals, a distinct respiratory-related rhythm, locked to that of phrenic nerve activity, was discerned. Thus, spontaneous activity of barosensory VLM neurons is inhibited by afferent inputs from aortic and carotid sinus baroreceptors, but is excited by incoming signals from carotid body chemoreceptors and the posterior hypothalamic area. It is also subject to the influence of the central mechanism generating the respiratory rhythm.

In urethane-anesthetized rabbits, 209 spontaneously active neurons that responded to stimulation of aortic nerve A fibers were found within the ventrolateral medulla (VLM). The neurons, termed barosensory VLM neurons, were inhibited, except for three instances, by stimulation of A fibers. Forty-seven percent of barosensory VLM neurons tested (74 of 159) were activated antidromically by electrical stimulation of the dorsolateral funiculus at the C2 level. Activity of barosensory VLM neurons was enhanced by stimulation of carotid body chemoreceptors or the posterior hypothalamic area, whereas it was diminished by increases in arterial pressure elicited by injection of phenylephrine. Barosensory VLM neurons responded variously to stimulation, with two to three pulses at 40 or 100 Hz, of spinal afferents of cutaneous and muscle origins and the spinal trigeminal complex. Although stimulation of one group of somatosensory fibers could evoke different patterns of neuronal responses consisting of excitatory and inhibitory components, the following responses were most often encountered. Group II cutaneous afferents caused an inhibition. Recruitment of group III afferents brought about a brief excitatory component preceding it. Activation of group IV cutaneous fibers added a long latency excitatory component. Excitation of groups III and IV muscle afferents most often resulted in an inhibition, whereas stimulation of the spinal trigeminal complex elicited various combinations of excitatory and inhibitory components. These results are consistent with the view that neurons in the ventrolateral medulla receive barosensory and nonbarosensory inputs from various peripheral and central sources and participate in the control of sympathetic vasomotor activity and arterial pressure.

In urethane-anesthetized and vagotomized rabbits, activation of C-fibers of renal afferents resulted in a reflex change in multifiber renal nerve activity (RNA) which consisted of inhibitory (I) and excitatory (E) components, either alone or in combination. The I and E components were individually and reversibly blocked by bilateral application of bicuculline and kynurenic acid, respectively, to the ventral surface of medulla. Bicuculline further eliminated the sympathoinhibiton produced by stimulation of the aortic nerve. Within the subjacent rostral ventrolateral medulla (RVLM), we recorded 23 spontaneously active single units that responded to electrical stimulation of renal afferents and were antidromically activated by stimulation of the dorsolateral funiculus at the C2 level. Usually, the neuronal response preceded that of the RNA by about 100 ms. These bulbospinal RVLM neurons were barosensory, since they responded to stimulation of the aortic nerve. We conclude that barosensory neurons in the RVLM mediate the renal-sympathetic reflex in rabbits.