Excitatory amino acid receptor blockade within the caudal pressor area and rostral ventrolateral medulla alters cardiovascular responses to nucleus raphe obscurus stimulation in rats

Pressor responses elicited by stimulation of the nucleus raphe obscurus (NRO) depend on the integrity of the rostral ventrolateral medulla (RVLM). Therefore, to test the participation of excitatory amino acid (EAA) receptors in the cardiovascular responses evoked by NRO stimulation (1 ms, 100 Hz, 40-70 æA, for 10 s), the EAA antagonist kynurenic acid (Kyn) was microinjected at different sites in the ventrolateral medullar surface (2.7 nmol/200 nl) of male Wistar rats (270-320 g, N = 39) and NRO stimulation was repeated. The effects of NRO stimulation were: hypertension (deltaMAP = +43 ± 1 mmHg, P<0.01), bradycardia (deltaHR = -30 ± 7 bpm, P<0.01) and apnea. Bilateral microinjection of Kyn into the RVLM, which did not change baseline parameters, almost abolished the bradycardia induced by NRO stimulation (deltaHR = -61 ± 3 before vs -2 ± 3 bpm after Kyn, P<0.01, N = 7). Unilateral microinjection of Kyn into the CVLM did not change baseline parameters or reduce the pressor response to NRO stimulation (deltaMAP = +46 ± 5 before vs +48 ± 5 mmHg after Kyn, N = 6). Kyn bilaterally microinjected into the caudal pressor area reduced blood pressure and heart rate and almost abolished the pressor response to NRO stimulation (deltaMAP = +46 ± 4 mmHg before vs +4 ± 2 mmHg after Kyn, P<0.01, N = 7). These results indicate that EAA receptors on the medullary ventrolateral surface play a role in the modulation of the cardiovascular responses induced by NRO stimulation, and also suggest that the RVLM participates in the modulation of heart rate responses and that the caudal pressor area modulates the pressor response following NRO stimulation

Pressor effects elicited by stimulation within the medullary raphe nuclei of the guinea pig (Cavia porcellus)

The medullary raphe nuclei are involved in central autonomic regulation. In all species investigated, electrical stimulation of the raphe nuclei causes cardiovascular responses, although, these changes vary between species. The present study was designed to investigate the participation of these nuclei in cardiovascular regulation in the guinea pig. We studied the effect on arterial blood pressure (BP) and heart rate (HR) of electrical stimulation (isolated cathodal square wave pulses for 10 s at 100 Hz, 40-100 muA and 1-ms pulse duration) within the medullary raphe nuclei in urethane-anesthetized (1.2g/kg, i.p.) guinea pigs (400-600g. either sex). Electrical stimulation of the same sites was performed on a group of paralyzed (Flaxedil®, 1 mg/kg, i.v.) and artificially ventilated animals. Stimulation sites were histologically defined and maps of the stimuli were obtained for the effect of electrical stimulation on arterial blood pressure. In another series of experiments, L-glutamate (0.2 M) was microinjected (75 to 150 nl) into the nucleus raphe obscurus. Electrical stimulation of the raphe nuclei produced predominantly pressor responses (delta= +15 to +100 mmHg: 43 percent of the stimulated sites). Hypotension (delta= -10 to -25 mmHg, 24 percent of the stimulated sites), biphasic responses (2 percent) or no change in BP (31 percent) were evoked from fewer stimulation sites. Pressor responses were also predominant in paralyzed animals (delta= +15 to +95 mmHg; 47 percent of the stimulates sites), and after microinjection of L-glutamate into the raphe obscurus (A= +20 to +45 mmHg). The present results demonstrate that in the guinea pig the stimulation of these nuclei evokes mainly pressor responses. These responses are similar to those obtained in the rat and hamster but opposite to those observed in the cat and rabbit.

Pressor effects elicited by stimulation within the medullary raphe nuclei of the golden hamster (Mesocricetus auratus)

The medullary raphe nuclei are involved in central autonomic regulation. In all species investigated, electrical stimulation of the raphe nuclei causes cardiovascular responses, although these changes vary between species. The present study was designed to investigate the participation of these nuclei in cardiovascular regulation in the hamster. We studied the effect on arterial blood pressure (BP) and heart rate (HR) of electrical stimulation (isolated cathodal square wave pulses for 10 sec at 100 Hz, 40-100 muA and 1-msec pulse duration) within the medullary raphe nuclei in urethane-anesthetized (1.2 g/kg, iv, after ether induction) golden hamsters (Mesocricetus auratus, 130 to 150 g, either sex). Electrical stimulation of the same sites was performed on a group of paralysed (Flaxedi1(, 1 mg/kg, iv) and artificially ventilated animals. Stimulation sites were histologically defined and maps of the stimuli were obtained for the effect of electrical stimulation on arterial blood pressure. In another series of experiments L-glutamate (0.18 M) was microinjected (75 to 150 nl) into the nucleus raphe obseurus. Electrical stimulation of the raphe nuclei produced predominantly pressor responses (delta =+ 12 to + 100 mmHg; 49.3 per cent of the stimulated sites). Hypotension (delta =-5 to -20 mmHg; 14.6 per cent of the stimulated sites) and no change in BP (35.3 per cent) were evoked from fewer stimulation sites. Pressor responses were also predominant in paralysed animals (delta =+ 15 to + 95 mmHg; 62.5 per cent of the stimulated sites), and after microinjection of L-glutamate into the raphe obscurus (delta = +35 to + 135 mmHg). The present results demonstrate that in the hamster the stimulation of these nuclei evokes mainly pressor responses. These responses are similar to those obtained in the rat and guinea pig but opposite to those observed in the cat and rabbit.

A comparison of the effects of eserine sulfate on the activity of medullary raphe neurons in the anesthetized rabbit and rat

1. Medullary raphe neurons are involved in the control of sympathetic activity during desynchronized sleep (DS). Eserine sulfate induces a state with the somatic and visceral signs of DS in decerebrate animals. The rabbit and rat display diverse hemodynamic patterns during DS. 2. To determine whether eserine sulfate provokes different responses in the medullary raphe neuron population of these different species, the drug (100 mg/kg, i.v.) was administered to urethane-anesthetized (1.2 g/kg, i.v.) rabbits (1.5-3.0 kg) and rats (Wistar, 260-310 g). 3. Extracellular activity was recorded from 66 neurons in 30 rats. Cholinergic stimulation provoked an increase in discharge rate (DR) in 45 neurons (68), a decrease in 8 neurons (12) and no change in 13 neurons (20). Recordings were obtained from 30 neurons in 11 rabbits. Stimulation of these cells provoked an increase in DR in 17 neurons (57), a decrease in DR in 7 neurons (23) and no change in 6 neurons (20). Interspike interval and auto-correlation analysis was performed on 28 rat and rabbit neurons. No significant difference was found between the rat and the rabbit with respect to the number of the neurons which were either inhibited or excited by cholinergic stimulation (P > 0.05). Similarly, unit response to eserine was not related to whether the unit displayed regular or irregular DR. 4. Therefore, we suggest that the diverse hemodynamic patterns during DS and the distinct cardiovascular responses to raphe nuclei stimulation are not due to differences in the organization of the raphe nuclei themselves but to differences in their axonal projections or in the postsynaptic receptors activated in the intermediolateral cell column or other postsynaptic targets.

Participation of nucleous raphe obscurus in the control of sympathetic activity in the anesthetized rat

The medullary raphe are involved in the control of sympathetic activity during desynchonized sleep and in the modulation of nocicepotive sensory inpts. To determine the particpation cholinergic and opiate mechanisms in the control of sympathetic activity, we microinjected eserine, morphine and naloxone into the nucleus raphe obscurus (NRO) of urethane-anesthetized rats. Arterial blood pressure (BP) and renal nerve activity (RN) were recorded. Eserine and morphine induced significant reductions of RN and BP, while naloxone had no effect. It is suggested that cholinergic and opiate mechanisms particpate in the control of sympathetic activity by th NRO

Responses of neurons of the nucleus raphe obscurus to noxious stimuli

Extracellular recordings were made from neurons located in the nucleous raphe obscurus (NRO), raphe magnus (NRM), and raphe pallidus (NRP) of urethane-anesthetized rats. Noxious cutaneous stimuli had excitatory, inhibitory or no effect on neurons of the nuclei. Most of the neurons were excited by noxious stimuli. The distribution of responses of noxiously activated units in the NRO is similar to that observed in the NRM. It is suggested that the NRO is also a component of the endogenous pain suppression system that originates in the NRM

Effects of physostigmine on the activity of medullary raphe neurons in anesthetized rats

Medullary raphe neurons are involved in the control of sympathetic activity during desynchronized sleep. To determine if cholinergic simulation of these sites has any effect on raphe unit activity, we administered physostigmine to urethane'anesthetized rats. Most of the neurons (68%) were excited by physostigmine, suggesting the existence of cholinergic synapses which are excitatory for the majority of medullary raphe neurons