Aortic Nerve Research Articles

Activity of aortic chemoreceptors in the anaesthetized rat.

1. It has been widely accepted that the rat aortic depressor nerve contains only baroreceptors. However, the experiments which have provided these negative data have employed whole aortic nerve recording. In the present study, the technical difficulties associated with recording single fibres in vivo, from the rat aortic nerve (diameter 25-50 microm), have been surmounted using a small tip, glass suction electrode technique. 2. Upon switching from normocapnic hyperoxia to hypercapnic hypoxia, irregularly firing units (n = 13) appeared and these were significantly excited by intravenous injections of sodium cyanide (20 microg) but not by rises in arterial blood pressure induced by methoxamine (an alpha1-adrenoreceptor agonist; 10 microg). Inhalation of 100 % oxygen rapidly and reversibly silenced, or profoundly reduced, ongoing activity. 3. Intravenous injection of phenylbiguanide (PBG; a 5-HT3 receptor agonist; 8 microg) strongly stimulated the chemoreceptors and was followed by a period of chemodepression (3-21 s). In contrast none of the single fibre baroreceptors recorded (n = 15) were excited by PBG but all significantly increased their discharge in response to the increases in arterial blood pressure associated with methoxamine and cyanide. Both the excitatory and inhibitory effects of PBG on the chemoreceptor fibres were abolished by ondansetron (a 5-HT3 receptor antagonist: 1 mg kg-1 i.v.; n = 5 animals) whilst the chemoexcitatory action of cyanide was preserved. 4. It is concluded that there are chemoreceptor afferents contained in the aortic nerve of the Sprague-Dawley rat. The 5-HT3 receptor appears not to be a pre-requisite for aortic body chemoexcitation.

Inhibition of baroreflex vagal bradycardia by nasal stimulation in rats.

Nasal stimulation provokes hypertension and bradycardia. We report here that such stimulation inhibits baroreflex vagal bradycardia (BVB). In chloralose- and urethan-anesthetized, beta-adrenergic receptor-blocked rats, the aortic depressor nerves were cut and electrically stimulated to induce BVB. Nasal application of smoke, warm distilled water, or cold or hot Ringer solution suppressed BVB, but application of warm Ringer solution did not. Smoke-induced inhibition was abolished by trigeminal but not olfactory denervation. Neither suprapontine decerebration nor C3 spinal cord transection affected the inhibition. Bradycardia induced by electrical stimulation of the peripheral cut end of the cervical vagus nerve (VIB) was suppressed by long-lasting smoke application. Intravenous prazosin, a proposed blocker of prejunctional inhibition of acetylcholine release from the vagus terminals, abolished VIB inhibition but attenuated BVB inhibition only slightly. Thus nasal stimulation inhibits BVB, and this inhibition is mediated exclusively by the trigeminal nerve and occurs principally at the pontomedullary level, although the potential exists for contribution of the prejunctional mechanism. The inhibition of BVB might contribute to cardiovascular regulation associated with protection from atmospheric hazards.

Excitatory and Inhibitory Responses of the Ongoing Sympathetic Discharge in Single Renal Neurons to Liminal Stimulation of Aortic C-Fibres in the Rabbit

Excitatory and inhibitory responses of sympathetic discharge were recorded in single renal postganglionic neurons of rabbits anaesthetized with urethane and chloralose. The animals were vagotomized and had transected aortic nerves. Responses were elicited by single volleys in the aortic C-fibres. Excitatory responses consisted in short-lasting increase in the rate of ongoing sympathetic discharge and were followed by inhibitory responses. Excitatory effects together with inhibitory responses were seen in 68% of units (19/28). Only excitatory effects appeared in 2 neurons (7.1%) and only inhibitory effects in 7 neurons (25%). In renal neurons exhibiting both effects, the excitatory responses appeared after latency of 172 ± 8 ms (x ± S.D.) and had duration of 64 ± 11 ms. Inhibitory effects had latency o f 257 ± 10 ms and their duration amounted to 265 ± 22 ms. In more than half of recordings the excitatory responses were separated from the inhibitory effects by discharge lasting 33 ± 4 ms. Significant correlations between latencies of excitatory and inhibitory responses and between duration of excitatory and latency of inhibitory responses suggest interaction between both effects. Increase in the number of afferent volleys (1 through 5) evoked relatively small changes in duration of the excitatory effect indicating that temporal facilitation is of minor importance in generating this response. Temporal facilitation was found to play an important role in determining duration of the inhibitory response. Comparison of effects of unilateral and bilateral stimulation of the aortic C-fibres showed larger occlusion of durations of the excitatory than inhibitory responses.

Rapid effects of corticosterone on cardiovascular neurons in the rostral ventrolateral medulla of rats

The present study has explored possible fast actions of corticosteroid hormones on activity of cardiovascular neurons of the rostral ventrolateral medulla. Experiments were conducted in 60 urethane-anesthetized, artificially ventilated adult rats. Extracellular recordings of unitary firings were made from the RVLM with multi- or single-barreled microelectrodes. Barosensitive cardiovascular neurons were identified through activation of the baroreceptor reflex by electrical stimulation of the aortic nerve and by intravenous injection of phenylephrine. In 52 barosensitive cardiovascular neurons, iontophoretically applied corticosterone sulfate increased the ongoing activity of 30 (57.7%) neurons, the other 22 (42.3%) neurons being unaffected. In 16 bulbospinal pre-sympathetic neurons, iontophorized corticosterone increased the firing rate of 12 neurons. Intravenously applied corticosterone (0.2 mg) increased the firing rates of 5 out of 12 bulbospinal pre-sympathetic neurons. The average baseline activity of cardiovascular neurons sensitive to corticosterone was found to be significantly less than that of the cardiovascular neurons insensitive to corticosterone. In 64 non-cardiovascular neurons, the firing rate of 13 (20.3%) neurons increased, 23 (36.0%) decreased and 28 (43.7%) remained unchanged following local application of corticosterone. The changes in firing rates of RVLM neurons following application of corticosterone occurred rapidly and were dependent on the doses of the agent. RU-38486 was able to reduce or block the rapid effects of corticosterone on cardiovascular and non-cardiovascular neurons. The results demonstrated that corticosterone may fast, non-genomically, modulate the activity of central regulators of the cardiovascular system and suggested that fast non-genomic actions of corticosteroid hormones may be an important mechanism in the integration of the autonomic nervous and the cardiovascular systems during some conditions such as stress.

Arterial baroreceptor afferent activity in nonpulsatile systemic circulation.

We directly measured aortic depressor nerve activity (ADNA) in rabbits to investigate changes in arterial baroreceptor afferent activity (ABAA) in response to nonpulsatile systemic circulation (NC) during total left heart bypass (TLHB). ADNA was measured before and 5, 20, 30, 40, 50, and 60 min after the start of TLHB while maintaining the mean aortic pressure (MAP) at preestablished values (n=10). At 5 min, the ADNA was significantly increased compared to its baseline value. At 30 min, it was significantly decreased compared to its value at 5 min and thereafter remained the same. The ADNA was then measured before and 5 and 30 min after the start of TLHB under increased MAP (n=10). The results showed that the percentage changes in ADNA during TLHB were significantly less than that observed when the MAP was increased before TLHB. We conclude that ABAA acutely adapts to NC 30 min after its initiation, but changes in ABAA are depressed under NC combined with increased MAP.

Evidence that NMDA receptors mediate the responses of putative RVLM presympathetic neurons to vagal afferent stimulation in rats

Experiments were performed in 25 urethane-anaesthetized male Sprague–Dawley rats. Forty-six RVLM neurons were identified as putative presympathetic neurons according to their arterial baroreceptor reflex related properties, i.e. they were inhibited by stimulation of the aortic nerve; silenced by elevation of blood pressure and had a cardiac cycle related rhythm of spontaneous discharge. Responses of these neurons to tripled square wave stimulation of vagal afferents was tested by means of peristimulus time histograms. In addition to a long-lasting inhibition (I 2), some neurons had one (P o) or two excitatory peaks (P 1 and P 2), and there was a short-lasting inhibition (I 1) between P 1 and P 2. After microinjection of CPP (0.1 μl, 50 mM) into the NTS, the inhibitory responses were blocked, but the excitatory peaks were not affected; in the CVLM, CPP microinjection of the same dose had a similar effect on the responses elicited by vagal afferent stimulation in 15 of the 24 neurons tested. No detectable effects were observed in 9 neurons. However, intravenously administered ketamine attenuated or abolished these responses, either inhibitory or excitatory, in a dose dependent way. These results suggest: (1) an NMDA mechanism is involved in both the inhibitory and the excitatory responses. For the inhibitory responses, the involvement is both in the NTS and in the CVLM; for the excitatory responses, it is probably in the RVLM. (2) There may be a direct excitatory amino acid (EAA) pathway from the NTS to the RVLM.

Effects of aortic nerve stimulation on discharges of sympathetic neurons innervating rat tail artery and vein.

Activity was recorded from postganglionic sympathetic neurons (PSNs) innervating either the caudal ventral artery (CVA) or a lateral vein (LV) of the tail circulation of anesthetized rats. The study sought to determine whether sympathetic activity directed at the CVA and LV was influenced by cardiovascular mechanoreceptor afferents and whether this effect was differential. Cardiac rhythmicity was not a robust component of either CVA PSN activity or LV PSN activity. Stimulation of an aortic nerve with short trains was followed by a decreased probability of discharge in both CVA and LV PSNs that was followed by a series of peaks that showed a constant periodicity that was not significantly different from that revealed by autocorrelogram analysis over the same data set. The latter dominant periodicity is referred to in this and related previous publications as the T rhythm. Furthermore, blood volume expansion and long-train aortic nerve stimulation produced a significant decrease in the frequency of the T rhythm. It is concluded that the CVA and LV sympathetic activity can be influenced by inputs from cardiovascular mechanoreceptors and that this effect is mediated in part by a modulation of the T rhythm.

Peripheral neural modulation of endotoxin-induced hyperventilation.

To delineate the role of the peripheral neural reflexes involved in modulating hyperventilation during endotoxemia. A prospective, randomized, controlled, multigroup study. Research animal laboratory. Adult Sprague-Dawley rats (n=43; 354+/-24 g) of either gender. Eight rats received a sham operation on their vagus, carotid sinus, and aortic nerves before the administration of a saline vehicle to serve as the time control. In the endotoxin group, 11 rats received a sham operation before endotoxin challenge. The remaining 24 rats received bilateral vagotomy (n=8), perivagal capsaicin treatment (n=8), or denervation of peripheral chemoreceptors (n=8) before endotoxin challenge. After the breathing pattern returned to a steady state, endotoxin (L-4130, serotype 0111, B4 lipopolysaccharide; 50 mg/kg) was injected into the vein. The rat's respiration was then monitored continuously for 5 hrs or until the animal died. The respiratory rate and tidal volume did not change over the 5-hr observation period in the time control group. In the endotoxin group, the respiratory rate increased significantly from baseline (135.4%) 2 hrs after endotoxin challenge and increased persistently until the rats died. The tidal volume increased gradually to < or =132.8% of baseline 4 hrs after endotoxin challenge. Bilateral cervical vagotomy and perineural capsaicin treatment of the vagus nerves eliminated the tachypnea response to endotoxin injection. Denervation of the peripheral chemoreceptor accentuated the hyperventilation response to endotoxin, and resulted in the shortest survival time. Both lung vagal C-fiber afferents and peripheral chemoreceptors are involved in modulating the hyperventilation response after endotoxin challenge in rat models. Stimulation of vagal C-fiber afferents increased the respiratory rate. Conversely, the role of peripheral chemoreceptors was to restrain the hyperventilatory response and these receptors may play a protective role during endotoxemia.

Chronic isolation of carotid sinus baroreceptor region in conscious normotensive and hypertensive rats.

We have developed a chronic technique to isolate the carotid sinus baroreceptor region in the conscious rat model. Our technique, when used in conjunction with other methods, allows for the study of the control of arterial pressure, heart rate, and cardiac output by the carotid sinus baroreceptor reflex in conscious, unrestrained rats. The performance of our technique was evaluated in two strains: normotensive Sprague-Dawley (SD) rats and spontaneously hypertensive rats (SHR). Each rat was instrumented with an aortic flow probe and a catheter placed in the right femoral artery to monitor cardiac output and arterial pressure, respectively. The cervical sympathetic trunk and aortic depressor nerve were ligated and cut bilaterally, leaving vagus nerves intact. The right and left carotid sinuses were isolated using our new technique. We tested the open-loop function of the carotid sinus baroreceptor reflex system in the conscious rat after recovery from the isolation surgery. We found that changes in nonpulsatile carotid sinus pressure caused significant changes in arterial pressure, heart rate, and total peripheral resistance in both rat strains. However, the cardiac output responses differed dramatically between strains. Significant changes were seen in the cardiac output response of SHR, whereas no significant changes were observed in normotensive SD rats. We have found this technique to be a highly reliable tool for the study of the carotid sinus baroreceptor reflex system in the conscious rat.

Chronic AT1 receptor blockade alters aortic nerve activity in hypertension.

In the chronic phase of coarctation hypertension (CH) we have shown both reduction in baroreceptor sensitivity (Hypertension. 1992;19[suppl II]:II-198-II-201.) and normalization of the depressed baroreceptor reflex control of heart rate, even with the persistence of hypertension in losartan-treated animals (Am J Physiol. 1995;269:H812-H818). In the present study we analyzed the effects of angiotensin II blockade on afferent aortic nerve activity of CH and sham-operated groups treated chronically with vehicle or losartan (10 mg/kg per day p.o.). CH was induced by subdiaphragmatic aortic coarctation, and the treatments lasted 8 days (4 control and 4 experimental days). Aortic pressure (conscious rats) and aortic nerve activity simultaneous to pressure (anesthetized rats) were recorded on the fourth day of the experimental period. Losartan-treated rats showed reduced tail pressure (104+/-3 versus 117+/-3 mm Hg in the vehicle group). In both groups, aortic coarctation caused a significant increase in pressure (25% and 28%, respectively) and a depression of the aortic nerve activity/pressure relationship when compared with sham-operated coarcted animals. In the physiological range of pressure changes, the depression was significantly smaller after losartan treatment (3.30+/-0.33 versus 2.18+/-0.37%/mm Hg in the losartan- and vehicle-treated CH groups, respectively, versus 5.05+/-0.33%/mm Hg in the sham-operated vehicle-treated group). Angiotensin type 1 (AT1) receptor blockade was also accompanied by reduced variability of the afferent discharge. The data suggested that apart from its pressure effect, angiotensin II acts at AT1 receptors to decrease the sensitivity of aortic afferents during physiological (+/-10 mm Hg) increases and decreases in pressure. Thus, angiotensin II may contribute to reductions of baroreceptor gain in chronic hypertension.

Excitation of baroreceptors depresses A- and C-components of the somato-cardiac sympathetic reflex in anesthetized rats.

The effect of baroreceptor activation on somato-cardiac sympathetic reflex discharges was examined in urethane-anesthetized, vagotomized, and artificially ventilated rats. Single shock stimulation of myelinated (A) and unmyelinated (C) fibers in the tibial nerve of the left hindlimb elicited two separate excitatory reflex discharge components in a branch of the cardiac sympathetic nerve. They are termed the A- and C-components of the somato-cardiac sympathetic reflex discharges. When aortic nerves (AN) and carotid sinus nerves (CSN) were intact, a sudden increase in mean arterial blood pressure to about 150 mmHg induced by I.V. injection of phenylephrine (50 micro/kg) depressed the A- and C-components by up to 47 +/- 5.4 and 37 +/- 7.7% of the control values, respectively. However, bilateral sino-aortic denervation completely abolished the pressure-induced depression of both components. We conclude that baroreceptor afferent signals from the AN and CSN inhibit both A- and C-components of the excitatory somato-cardiac sympathetic reflex discharges. This and other previous evidence mentioned in the text indicate that inhibitory cardiac sympathetic reflexes originating from arterial baroreceptors and excitatory ones originating from somatic afferents interact, probably at the brainstem.

Dynamic transduction properties of in situ baroreceptors of rabbit aortic depressor nerve.

We developed a new method for isolating in situ baroreceptor regions of the rabbit aortic depressor nerve (ADN) and estimated the transfer function from pressure to afferent nerve activity in the frequency range of 0.01-5 Hz by a white noise technique. Complete isolation of the baroreceptor area of the right ADN was made in situ by ligation of the innominate artery and the right subclavian and common carotid arteries. We altered the pressure in the isolated baroreceptor area according to a binary quasi-white noise between 80 and 100 mmHg in 12 urethan-anesthetized rabbits. The gain increased two to three times as the frequency of pressure perturbation increased from 0.01 to 2 Hz and then decreased at higher frequencies. The phase slightly led below 0.2 Hz. The squared coherence value was > 0.8 in the frequency range of 0.01-4 Hz. The step responses estimated from the transfer function were indistinguishable from those actually observed. We conclude that the baroreceptor transduction of the ADN is governed by linear dynamics under the physiological operating pressure range.

Baroreceptor Activation Causes Release of Acetylcholine in the Rostral Ventrolateral Medulla of the Rat

We examined whether baroreceptor activation causes a release of acetylcholine (ACh) in the rostral ventrolateral medulla (RVLM) of the rat, in order to investigate a possible connection between RVLM cholinergic systems and cardiovascular baroreflexes. Male Wistar rats were anesthetized, paralyzed and artificially ventilated. Either electrical stimulation of aortic nerve or baroreceptor activation by intravenous phenylephrine produced an increase of the release of ACh in the RVLM, whereas baroreceptor denervation and tetrodotoxin (TTX) microinfusion in the RVLM inhibited the increase in ACh release induced by phenylephrine. TTX injected in the caudal ventrolateral medulla (CVLM) inhibited the phenylephrine-induced increase of ACh release. The excitatory amino acid L-glutamate microinfused in the CVLM produced an release in ACh release in the RVLM. These results suggest that there is a connection between RVLM cholinergic systems and cardiovascular baroreflexes. It is probable that neurons in t h e CVLM are involved in mediating the release of ACh in the RVLM

A laser confocal microscopic study of vagal afferent innervation of rat aortic arch: Chemoreceptors as well as baroreceptors

Although the aortic nerves contain vagal afferents that terminate in both the wall of the aortic arch (putative baroreceptors) and its associated glomus tissue (putative chemoreceptors) in most mammalian species, the aortic nerves of the rat have been widely assumed to contain only baro- or pressor afferents. The present study reconsidered this anomaly by characterizing vagal afferent endings and their targets in the aortic arch region of the rat, both qualitatively and quantitatively. Eight Sprague–Dawley rats received intracranial vagal motor rhizotomy unilaterally to eliminate efferents in the nerve and then, two weeks later, injections of the tracer DiI (1,1′-dioleyl-3,3,3′,3′-tetramethylindocarbocyanine methanesulfonate) into the ipsilateral nodose ganglion. The aortic arch and its surrounding tissue, with the common carotid and subclavian arteries attached, were examined with both conventional epifluorescence and confocal microscopes. Consistent with earlier observations, vagal afferents formed both flower-spray and end-net terminals rather diffusely within the wall of the aortic arch. More interestingly, vagal afferents also innervated glomus or SIF (i.e., small intensely fluorescent) cell bodies at the junction areas of the common carotid and subclavian arteries. To identify the course of these fibers, six additional animals received DiI injection into the nodose unilaterally after a complete cervical vagotomy caudal to the nodose; in these animals, the aortic nerve had been separated from the vagal trunk and kept intact. There were no marked differences in innervation patterns between the nonvagotomized and the cervically vagotomized animals, indicating that the vagal axons innervating the walls of the blood vessels and the SIF cells in the aortic arch region travel through the aortic nerves. Using a stereological method, we estimated the relative number of chemo- and baroreceptor afferents innervating the aortic arch. About 16.4% (left) and 13.1% (right) of fibers in the aortic nerves innervate SIF cells. These findings challenge the general consensus that the aortic nerves of rats contain exclusively baroreceptor fibers.

Chronopharmacology. Time of day variations in the action of bupivacaine are not manifested in nerves

To test the hypothesis that the efficacy of local anaesthetics to block nerve conduction is related the time of day (TOD) of drug application, we retrospectively analysed data from previous experiments on tachyphylaxis. During the course of these experiments, as a measure of drug efficacy we determined the minimal blocking concentration (c(m)) of bupivacaine in rabbit aortic nerves at several TODs. The special in situ preparation used permitted study of local anaesthetic pharmacodynamics without the influence of pharmacokinetics, making it possible to investigate the chronopharmacodynamics of these drugs by relating c(m)s to the respective TODs of their measurement. In 43 New Zealand rabbits anaesthetised with urethane, the aortic nerve was dissected and partly placed in a double-lumen perfusion chamber (Fig. 1A), which was continuously perfused with tyrode solution or bupivacaine. Spike activity was continuously recorded by bipolar platinum-iridium electrodes caudad to the chamber for control and cephalad for registration of blocking effects. As a measure of drug efficacy, by increasing the bupivacaine concentration stepwise we determined the smallest concentration that blocks spike activity i.e., c(m). After each determination bupivacaine was rinsed off to confirm intact nerve function (Fig. 18). Forty-nine determinations of bupivacaine c(m) were performed between 12:25 p.m. and 2:35 a.m. Data were pooled into groups of 2 h (Fig. 2). There was no significant difference between groups (ANOVA). In particular, c(m) at 3:00 p.m. was not lower than at 11:00 p.m., times at which local anaesthetics have been found to be most and least effective, respectively. The c(m) of bupivacaine, and thus its efficacy to block nerve conduction, does not depend on TOD of drug application. Therefore, it is suggested that chronopharmacodynamics does not play an important role in the well-known circadian rhythm of the action of bupivacaine and probably of local anaesthetics in general.

Cardiovascular afferent inputs to ventral tegmental area.

Extracellular single-unit recording experiments were done in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated rats to investigate the effect of selective activation of arterial baroreceptors and stimulation of cardiovascular depressor sites in the nucleus of the solitary tract (NTS) on the discharge rate of neurons in the ventral tegmental area (VTA). Electrical stimulation of the aortic depressor nerve (ADN), which is known to carry aortic baroreceptor afferent fibers only, excited 12 of 21 (mean onset latency 42.4 +/- 8.8 ms) and inhibited 2 of 21 (mean onset latency 42.5 +/- 6.5 ms) single units in the VTA. The discharge rate of VTA units was also altered during the reflex activation of arterial baroreceptors by the acute rise in arterial pressure (AP) to systemic injections of phenylephrine (10 micrograms/kg i.v.): 12 of 44 units were excited and 15 of 44 were inhibited. Units that responded to either ADN stimulation or the reflex activation of the baroreflex also responded to stimulation of depressor sites in the NTS. An additional 12 units that were found in barodenervated controls to be responsive to NTS stimulation were nonresponsive to selective activation of arterial baroreceptors. These data indicate that cardiovascular afferent inputs modulate the activity of neurons in the VTA and suggest that changes in systemic AP may exert an effect on the activity of neurons involved in mesolimbic and mesocortical function.

Role of AMPA/kainate receptors in transmission of the sympathetic baroreflex in rat CVLM.

We examined the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors within the caudal ventrolateral medulla (CVLM) in mediating the sympathetic baroreceptor reflex in anesthetized and paralyzed rats. Bilateral microinjection into CVLM of either DL-2-amino-5-phosphonovaleric acid [APV; a selective N-methyl-D-aspartic acid (NMDA) receptor antagonist, 20 mM, 100 nl] or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; a selective AMPA/kainate receptor antagonist, 2 mM, 100 nl) alone failed to eliminate the aortic nerve stimulation-evoked hypotension and inhibition of splanchnic sympathetic nerve activity (SNA) or the cardiac-related rhythmicity of SNA. All components of the sympathetic-baroreceptor reflex were abolished when kynurenate (100 mM, 30 nl) or mixtures of APV and CNQX (10 and 1 mM, respectively, 100 or 30 nl) were injected into CVLM. Injection of APV or CNQX into CVLM reduced aortic nerve-evoked inhibitory responses of bulbospinal sympathoexcitatory neurons in rostral ventrolateral medulla (RVLM). The extent of this reduction was variable. Usually, significant inhibition was preserved. In seven RVLM neurons, intravenous injection of MK-801 (NMDA receptor antagonist, 2 mg/kg) failed to eliminate aortic nerve-evoked inhibitory responses. However, inhibitory responses were abolished when CNQX was injected into CVLM after intravenous MK-801. We conclude that both NMDA and AMPA/kainate receptors in CVLM transmit baroreceptor information.

Administration of AVP to the area postrema alters response of NTS neurons to afferent inputs.

This study was designed to determine if arginine vasopressin (AVP) facilitates the response of nucleus of the solitary tract (NTS) neurons to baroreceptor input. In anesthetized sinoaortic-denervated vagotomized rabbits, AVP was intravenously infused (15 microg x kg(-1) x min(-1), 1 min) or microinjected into the area postrema (AP; 1 ng/nl, 10 nl). Extracellular recordings of evoked NTS neuronal responses to electrical stimulation of the aortic depressor nerve (ADN) or vagus nerve (1 Hz, 2-20 V, 0.05-0.6 ms) were evaluated before and after AVP administration. In neurons receiving input from the ADN (n = 19), 58% of them increased their responses after AVP (40.3 +/- 5.0 to 71.5 +/- 4,8%, P < 0.001). Similarly, in neurons activated by vagal stimulation (n = 22), 55% of them were facilitated during AVP administration (59.7 +/- 12.8 to 90.8 +/- 10.7%, P < 0.01). This action of AVP was independent of the mode of AVP administration, since either microinjection or venous infusion was effective in augmenting responses of NTS neurons to aortic/vagal stimulation. In an additional 37 spontaneous NTS neurons, AVP showed no effect on the mean baseline firing rate (8.9 +/- 1.3 vs. 9.6 +/- 1.3 spikes/s, P > 0.05), but increased neuronal activity in 54% of neurons (6.9 +/- 1.3 vs. 13.1 +/- 1.7 spikes/s, P < 0.01). In two rabbits pretreated with vasopressin antagonist (15 microg/kg iv), AVP failed to produce facilitatory effects (n = 8). The results of this study provide evidence in support of the hypothesis that circulating peptides modulate the arterial baroreflex via activation of neurons in the AP.

Effects of combined carotid sinus and aortic depressor nerve denervations in neonatal rat pups.

Denervation of the major peripheral chemo- and barosensory organs of neonatal mammals is known to produce age-dependent effects on mortality and on respiratory and cardiovascular functions. In the current series of experiments, these phenomena were more fully characterized in the young rat. 8- to 9-day-old rats showed few effects of combined carotid sinus and aortic depressor nerve (CSAD) denervation. During the days following surgery, these animals maintained normal body temperatures, had relatively normal weight gain, little cardiorespiratory disruption, and none died. Denervation at earlier ages (postnatal days 3-4 or 0-1) resulted in considerable mortality, 24 and 59%, respectively. In addition, body temperatures were lower, and the weight gain was impaired in the denervated pups as compared with controls, and these effects were more severe in the CSAD nonsurvivors than in the survivors. Also, nonsurvivors had much more severe disruptions of cardiorespiratory patterns measured 24-96 h after surgery than did CSAD survivors. Twenty-four hours after surgery, pups that later died could be identified based on low heart rates and long inspiratory times. CSAD survivors maintained a pattern of moderate cardiorespiratory disruption as compared with controls. Finally, our results indicate that the additional stress of subcutaneous electrocardiography lead implantation and/or daily maternal separation for cardiorespiratory recording increased the mortality in the 3- to 4-day-old CSAD pups from 11 to 40%.

Is L-Dopa a Neurotransmitter of the Primary Baroreceptor Afferents Terminating in the Nucleus Tractus Solitarii of Rats?

Transmitter-like Dihydroxyphenylalanine (DOPA) is released from rat striata and blood pressure regulation centers in the lower brain stem. Exogenous DOPA itself elicits in vitro presynaptic and in vivo postsynaptic responses. All are stereoselective, and most are antagonized by DOPA methyl ester, a competitive DOPA antagonist. DOPA does not displace selective binding of α 2 , β , D 1 , and D 2 ligands in brain membrane preparations. It is possible to cooperate for effectiveness in Parkinson's disease. Meanwhile, DOPA induces DOPA ester-sensitive neuronal glutamate release from slices, even under inhibition of aromatic L-amino acid decarboxylase (AADC). The release by baroreceptor stimulation with phenylephrine has been abolished by bilateral sinoaortic denervation without modification of hypertension. DOPA microinjected into depressor sites of the medial nucleus tractus solitarii (NTS) identified by prior glutamate leads to dose-dependent decreases in blood pressure and heart rate (HR) in untreated rats and in those treated with central AADC inhibitor. The discussion also includes interactions between DOPAergic and GABAergic systems. GABA is an inhibitory neuromodulator for baroreflex at the level of NTS. GABA functions tonically via GABA A receptors to elicit increases in blood pressure and HR and to inhibit decreases in those by electrical aortic nerve stimulation. The third topic under discussion in this chapter is altered functions of the DOPA system in the NTS of adult spontaneously hypertensive rats (SHR). Basal DOPA release is lower in SHR than age-matched Wistar-Kyoto (WKY) rats. This release has been reduced by tetrodotoxin (TTX) to the same absolute levels in the two strains.