Renal Nerve Discharge Research Articles

Abstract 306: Alamandine but not angiotensin-(1-7) produces cardiovascular effects in the Insular Cortex

In the course of experiments aimed to evaluate the immunofluorescence distribution of MrgD receptors we observed the presence of immunoreactivity for the MrgD protein in the Insular Cortex. In order to evaluate the functional significance of this finding, we investigated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Urethane (1.4g/kg) anesthetized rats were instrumented for measurement of MAP, HR and renal sympathetic nerve activity (RSNA). Unilateral microinjection of alamandine (40 pmol/100nl), Angiotensin-(1-7) (40pmol/100nl), Mas/MrgD antagonista D-Pro7-Ang-1-7 (50pmol/100nl), Mas agonist A779 (100 pmol/100nl) or vehicle (0,9% NaCl) were made in different rats (N=4-6 per group) into posterior insular cortex (+1.5mm rostral to the bregma). Microinjection of alamandine in this region produced a long-lasting (> 18 min) increase in MAP (Δ saline= -2±1 vs. alamandine= 12±2 mmHg, p< 0.05) associated to increases in HR (Δ saline= 2±2 vs. alamandine= 35±5 bpm; p< 0.05) and in the amplitude of renal nerve discharges (Δ saline = -2±1 vs. alamandine= 35±5.5 % of the baseline; p< 0.05). Strikingly, an equimolar dose of angiotensin-(1-7) did not produce any change in MAP or HR (Δ MAP=-0.5±0.3 mmHg and +2.7±1.2 bpm, respectively; p> 0.05) and only a slight increase in RSNA (Δ =7.3±3.2 %) . In keeping with this observation the effects of alamandine were not significantly influenced by A-779 (Δ MAP=+13± 2.5 mmHg, Δ HR= +26±3.6 bpm; Δ RSNA = 25± 3.4%) but completely blocked by the Mas/MrgD antagonist D-Pro7-Ang-(1-7) (Δ MAP=+0 ± 1 mmHg Δ HR= +4±2.6 bpm; Δ RSNA = 0.5± 2.2 %). Therefore, we have identified a brain region in which alamandine/MrgD receptors but not Ang-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to Ang-(1-7) in the brain.

Mechanisms of depressor effect of norepinephrine injected into subnucleus commissuriu of nucleus solitarius tractus in rabbits.

This experiment aimed to investigate the effect of adrenergic system in the subnucleus commissuriu of nucleus solitrius tractus (CNTS) on renal nerve discharges. Norepinephrine (NE) was microinjected into the CNTS of rabbits and mean arterial blood pressure (MAP) and renal nerve discharges (FRND) were synchronously recorded. The results indicated that (1) microinjection of norepinephine into the CNTS of rabbit could significantly attenuate the frequency of renal nerve discharge, and at the same time decrease markedly the mean arterial pressure. (2) Microinjection of 0.3 nmol yohimbin into CNTS had no significant influence on FRND and MAP, but could attenuate and even reverse the effects of NE on FRND and MAP. These results suggest that microinjection of NE into CNTS may activate the alpha-adrenorecptor located in CNTS and secondarily produce a depressor effect by attenuating the activity of periphenal sympathetic nervous system.

Hypercapnia induces long-term changes in postganglionic renal nerve activity in the piglet

In developing swine, time and frequency domain analyses were used to compare changes in discharge features of efferent phrenic and postganglionic renal nerve activities evoked by prolonged (1 h) exposure to severe hypercapnia (10% CO 2, balance O 2), before and after combined carotid sinus and aortic depressor nerve (CSN–AOD) sectioning. With intact CSN–AOD innervation, respiration-related activity in renal nerve discharge was rare (3 of 11 animals) during baseline periods with intact innervation, but was observed in most cases (10 of 11 animals) during baseline following denervation. Renal nerve respiration-related activity was recruited by hypercapnic stimulation in animals with intact CSN–AOD innervation, and was augmented in denervated animals with ongoing respiratory activity. Phrenic nerve discharge was markedly augmented during hypercapnia, whether CSN–AOD innervation was intact or not, and it did not exhibit a post-hypercapnic depression. Autopower spectra of renal nerve activity revealed the presence of two coexisting rhythms, 2–6 and 7–13 Hz, which were present whether CSN–AOD innervation was intact or not. The hypercapnic-induced increases of activity in the 2–6 and 7–13 Hz bands were not comparable, with the latter region exhibiting a much more robust response to hypercapnia, especially following CSN–AOD denervation. Thus, prolonged exposure to hypercapnia evoked changes in renal nerve discharge that involved increased coupling to neuronal ensembles shaping central inspiratory activity and those generating central sympathetic outflows, especially to networks generating 7–13 Hz rhythm. Such changes may permit more efficient modulation of innervated structures during exposure to stressors.

Direct measurement of renal sympathetic nervous activity in high-fat diet-related hypertensive rats

The elevation of renal sympathetic nervous activity (SNA) is a possible cause of blood pressure (BP) elevation. Although a high-fat diet (FAT) often induces BP elevation in animals, the effect of FAT on renal SNA in animals is not consistent between studies. Thus, we compared the basal levels of efferent renal SNA and BP in FAT- or high-carbohydrate diet (CHO)-fed rats. Twenty-four male Sprague-Dawley rats were fed FAT (P/F/C=20/45/35% cal) or CHO (20/5/75) from 5 weeks of age. After 20–21 weeks of feeding, a 24-h urine sample was collected to measure sodium excretion. The next day, blood (0.2 ml) was withdrawn from a femoral artery, and basal efferent renal nerve discharges and mean arterial pressure (MAP) were recorded under anesthesia. Immediately after the experiment, abdominal (epididymal, perirenal and mesenteric) adipose tissues were dissected. Total abdominal fat weight was significantly greater in the FAT group than in the CHO group. The plasma level of leptin was significantly higher in the FAT group, but blood glucose and plasma insulin levels did not differ between the two groups. MAP and renal SNA were significantly higher in the FAT group. In addition, the ratio of urinary sodium excretion to dietary sodium intake was significantly lower in the FAT group than in the CHO group. The data suggest that the increased renal SNA may contribute to BP elevation in FAT-fed rats. The present study firstly demonstrated that renal SNA was elevated with FAT-related BP elevation.

Reduced endogenous GABA-mediated inhibition in the PVN on renal nerve discharge in rats with heart failure.

One characteristic of heart failure (HF) is increased sympathetic activation. The paraventricular nucleus (PVN) of the hypothalamus (involved in control of sympathetic outflow) has been shown to have increased neuronal activation during HF. This study examined the influence of endogenous GABA input (inhibitory in nature) into the PVN on renal sympathetic nerve discharge (RSND), arterial blood pressure (BP), and heart rate (HR) in rats with HF induced by coronary artery ligation. In alpha-chloralose- and urethane-anesthetized rats, microinjection of bicuculline (a GABA antagonist) into the PVN produced a dose-dependent increase in RSND, BP, and HR in both sham-operated control and HF rats. Bicuculline attenuated the increase in RSND and BP in HF rats compared with control rats. Alternatively, microinjection of the GABA agonist muscimol produced a dose-dependent decrease in RSND, BP, and HR in both control and HF rats. Muscimol was also less effective in decreasing RSND, BP, and HR in HF rats than in control rats. These results suggest that endogenous GABA-mediated input into the PVN of rats with HF is less effective in suppressing RSND and BP compared with control rats. This is partly due to the post-release actions of GABA, possibly caused by altered function of post-synaptic GABA receptors in the PVN of rats with HF. Reduced GABA-mediated inhibition in the PVN may contribute to increased sympathetic outflow, which is commonly observed during HF.

Effect of in vivo gene transfer of nNOS in the PVN on renal nerve discharge in rats.

The paraventricular nucleus (PVN) of the hypothalamus is known to be involved in the control of sympathetic outflow. Nitric oxide (NO) has been shown to have a sympathoinhibitory effect in the PVN. The goal of the present study was to examine the influence of overexpression of neuronal NO synthase (nNOS) within the PVN on renal sympathetic nerve discharge (RSND). Adenovirus vectors encoding either nNOS (Ad.nNOS) or beta-galactosidase (Ad.beta-Gal) were transfected into the PVN in vivo. Initially, the dose of adenovirus needed for infection was determined from in vitro infection of cultured fibroblasts. In Ad.nNOS-treated rats, the local expression of nNOS within the PVN was confirmed by histochemistry for NADPH-diaphorase-positive neurons. There was a robust increase in staining of NADPH-diaphorase-positive cells in the PVN on the side injected with Ad.nNOS. The staining peaked at 3 days after injection of the virus. In alpha-chloralose- and urethane-anesthetized rats, microinjection of N(G)-monomethyl-L-arginine (L-NMMA), a NO antagonist, into the PVN produced a dose-dependent increase in RSND, blood pressure, and heart rate. There was a potentiation of the increase in RSND, blood pressure, and heart rate due to L-NMMA in Ad.nNOS-injected rats compared with Ad.beta-Gal-injected rats. These results suggest that the endogenous NO-mediated effect in the PVN of Ad.nNOS-treated rats is more effective in suppressing RSND compared with Ad.beta-Gal-treated rats. These observations support the contention that an overexpression of nNOS within the PVN may be responsible for increased suppression of sympathetic outflow. This technique may be useful in pathological conditions know to have increased sympathetic outflow, such as hypertension or heart failure.

Blunted nitric oxide-mediated inhibition of renal nerve discharge within PVN of rats with heart failure.

We have demonstrated a decreased neuronal nitric oxide (NO) synthase (nNOS) message in the hypothalamus of rats with heart failure (HF). Subsequently, we have demonstrated that NADPH diaphorase (a commonly used marker for nNOS activity) positive neurons are decreased in paraventricular nucleus (PVN) of rats with coronary artery ligation model of HF. The goal of the present study was to examine the influence of endogenous NO within the PVN on renal sympathetic nerve discharge (RSND) during HF. In alpha-chloralose- and urethane-anesthetized rats, an inhibitor of NO synthase, N(G)-monomethyl-L-arginine (L-NMMA) microinjected into the PVN (50, 100, and 200 pmol in 50-200 nl) produced a dose-dependent increase in RSND, blood pressure, and heart rate in control and HF rats. These responses were attenuated in rats with HF compared with control rats. On the other hand, the NO agonist, sodium nitroprusside, microinjected in PVN produced a dose-dependent decrease in RSND and blood pressure in control and HF rats. These responses were less in rats with HF compared with control rats. These data suggest that the endogenous NO-mediated effect within the PVN of HF rats is less potent in suppressing RSND compared with control rats. These data support the conclusion that the NO system within the PVN involved in controlling autonomic outflow is altered during HF and may contribute to the elevated levels of renal sympathoexcitation commonly observed in HF.

Saccular and utricular influences on sympathetic nerve activities in cats.

We studied the effects of stimulation of the utricular and saccular nerves on sympathetic nerve activity in decerebrated cats. Bipolar electrodes were fixed in place on the utricular and/or saccular nerve under visual observation; the other branches of the vestibular nerve were transected. Baroreceptors and vagus nerves were inactivated bilaterally so that inputs from baroreceptors and other visceral receptors did not influence the sympathetic nerve outflow. Postganglionic sympathetic nerve activity was recorded from the renal branch of the sympathetic nerve, which is known to be more sensitive to vestibular stimuli than other types of sympathetic fibers. With stimulation of either the saccular or utricular nerve at low stimulus intensity, a prominent inhibition followed by a rebound excitation was evoked on spontaneous renal nerve discharges. The latency of the inhibition ranged from 65 to 130 ms, and the duration of inhibitory responses was about 90-150 ms. An increase in stimulus intensity in both the saccular and utricular nerves induced inhibitory effects preceded by short-term excitation. The latency of this excitation, which was superimposed on the initial phase of the inhibitory responses, ranged from 55 to 90 ms.

Effect of nitric oxide within the paraventricular nucleus on renal sympathetic nerve discharge: role of GABA.

Both nitric oxide (NO) and GABA are known to provide inhibitory inputs to the paraventricular nucleus (PVN) of the hypothalamus and are involved in the control of sympathetic outflow. The purpose of the present study was to examine the interaction of NO and GABA in the regulation of renal sympathetic nerve activity in rats. The responses of renal nerve activity, blood pressure, and heart rate to microinjection of sodium nitroprusside (SNP), an NO donor, into the PVN were measured in the presence and absence of blockade of the GABA system (bicuculline; 2 nmol). Microinjection of SNP (50, 100, and 200 nmol) into the PVN elicited significant decreases in renal nerve discharge, arterial blood pressure, and heart rate, reaching -36.4 +/- 9.7%, -11 +/- 5 mmHg, and -34 +/- 14 beats/min, respectively, at the highest dose. These responses were eliminated by blockade of the GABA system. Conversely, microinjection of Nomega-nitro-L-arginine methyl ester (L-NAME; 50, 100, and 200 nmol) elicited significant increases in the renal sympathetic nerve discharge, arterial blood pressure, and heart rate, reaching 88.9 +/- 16.6%, 9 +/- 1 mmHg, and 29 +/- 9 beats/min, respectively, at the highest dose. These sympathoexcitatory responses were masked by prior blockade of the GABA system with bicuculline. The sympathoexcitatory effect of L-NAME was also eliminated by activation of the GABA system with muscimol. In conclusion, our data indicate that the inhibitory effect of endogenous NO within the PVN on the renal sympathetic nerve activity is mediated by GABA.

Spinal cord segments mediating tonic sympathetic nerve discharge to the kidney in the anesthetized cat

According to anatomical data, preganglionic neurons projecting to the kidney via sympathetic ganglia occupy a wide range of adjacent segments in the thoracolumbar spinal cord, from Th7 to L2. Since, however, the majority of preganglionic neurons is silent at resting states, the active segments indeed transmitting sympathetic activity, at rest, may be different. In the present experiments, the spontaneous sympathetic activity was recorded before and after the sympathetic trunk and white rami (WR) Th8–L3 were cut in a sequential manner. The step-by-step changes in the power of renal nerve discharge were estimated and used for mapping tonic renal outflow to the spinal cord. We found that powerful activity comprising 70–95% of the power of control recordings remained after eliminating the input from Th1–Th12, indicating that thoracic spinal cord including segments that contain the largest number of cells projecting to renal postganglionic neurons contributes relatively weakly to tonic renal nerve activity. It appeared that resting sympathetic nerve discharge was predominantly maintained by the caudalmost division of the renal preganglionic neuron population since the largest decrease in nerve power occurred after severing WR Th13, L1, and L2. These findings suggest that the `active segmental map' of preganglionic neurons controlling a certain organ at rest does not necessarily match the distribution of the total population of neurons projecting to the same effector.

Baroreflex function in streptozotocin (STZ) induced diabetic rats

To determine whether the renal sympatho-inhibition and bradycardia in responses to acute increases in arterial pressure are altered in the diabetic state, the renal nerve discharge and heart rate were measured in streptozotocin (STZ) induced diabetic (DIA) rats. Integrated renal sympathetic nerve activity and heart rate were measured before and during an acute increase in blood pressure in anesthetized (Inactin 0.1 g/kg, i.p.) control (vehicle) and DIA rats (Sprague Dawley rats injected with STZ 65 mg/kg i.p.). Blood glucose levels were significantly elevated in the DIA group compared with the control group. Baroreflex changes in renal nerve activity and heart rate were not significantly different in the DIA rats compared with control rats at a time when the renal sympatho-inhibition in response to acute volume expansion was blunted in the diabetic rats. In addition, blocking the effect of elevated angiotensin II in diabetic rats with the converting enzyme inhibitor enalapril did not change the baroreflex function in DIA rats compared with control rats. However, administration of vasopressin failed to potentiate the baroreflex in diabetic rats as it did in normal control rats. This study demonstrates that (1) the baroreflex function is normal in STZ induced diabetic rats unlike the volume reflex during the early phase of the disease, (2) blockade of the AII system does not alter baroreflex function in diabetic rats and (3) vasopressin fails to potentiate the baroreflex in diabetic rats as it does in the euglycemic normal rats.

Parvocellular neurons of the paraventricular nucleus are involved in the reduction in renal nerve discharge during isotonic volume expansion

The parvocellular neurons of the paraventricular nucleus (PVN) of the hypothalamus are known to be involved in the control of central autonomic outflow. While the PVN is also known to be involved in the control of fluid-balance, most of the studies examining this nucleus have emphasized the magnocellular neurons, which are involved in the humoral control of fluid-balance and related hemodynamics. The present study took advantage of the differential sensitivity of these two cell types to kainic acid as a means of investigating the role of the parvocellular neurons in the reflex reduction of renal sympathetic nerve discharge (RSND) during acute isotonic volume expansion. Kainic acid (18 pmol), which destroys parvocellular but not magnocellular neurons in the PVN, was microinjected (20 nl) bilaterally at sites in and adjacent to the PVN 3–4 days prior to acute isotonic volume expansion. In anesthetized rats RSND decreased by 59% at the completion of acute isotonic volume expansion (10% of body weight) in the vehicle-injected control group; on the other hand, it decreased by 33% in the kainic acid-treated group. The effect of destruction of the parvocellular neurons on the baroreceptor reflex was also examined. Neither the renal nerve component (Δ%RSND/ΔAP), nor the heart rate component (ΔHR/ΔAP), of the baroreceptor reflex were different in the kainic acid-treated group (3.1 ± 0.4, and 1.1 ± 0.1, respectively) than in the vehicle-injected control group (2.9 ± 0.7, and 0.8 ± 0.1, respectively). We conclude that the parvocellular neurons of the PVN are an important synaptic relay site in the reflex arc that is activated during isotonic volume expansion, but not in the baroreceptor reflex.

PLASMA RENIN ACTIVITY DURING HYPOTENSIVE RESPONSES TO ELECTRICAL STIMULATION OF CAROTID SINUS NERVES IN CONSCIOUS DOGS

1. The interaction of electrical stimulation of the carotid sinus nerves (carotid sinus nerve stimulation, CSNS) with mechanisms of renin release was studied in conscious and unrestrained resting beagle dogs receiving a standardized diet (sodium intake, 4.5 mmol/kg bodyweight (bw); water intake, 91 mL/kg bw). 2. By CSNS, mean arterial blood pressure (MAP) was lowered for periods of 20 min to levels between 101 +/- 4 and 56 +/- 5 mmHg. 3. In another group of conscious dogs, renal perfusion pressure (RPP) was lowered to 95 +/- 4 mmHg for periods of 20 min by partial suprarenal aortic occlusion in order to assess the influence of a reduced RPP on plasma renin activity (PRA) without concomitant CSNS. 4. During CSNS, PRA increased markedly (> 100%) only when MAP was reduced below 75 mmHg. 5. With aortic constriction and an RPP of 95 mmHg, the increase in PRA was 955%, which is more than three-fold higher than the increase in PRA during CSNS at MAP levels < 65 mmHg (314%). 6. The observed responses indirectly support the hypothesis that basal activity in efferent renal nerve discharge is present even at rest and can be inhibited by CSNS, and furthermore suggests that CSNS attenuated the pressure-dependent renin release.

Connections between the pontine reticular formation and rostral ventrolateral medulla

Pontine reticular formation (PRF) neurons provide tonic excitatory drive to sympathetic nerves and are involved in cardiovascular control [K. Hayes and L. C. Weaver. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1567-H1575, 1992]. However, connections between the PRF and the well-known vasomotor region in the rostral ventrolateral medulla (RVLM) are unknown. In propofol (Diprivan)- anesthetized rats we investigated arterial pressure, heart rate, and renal nerve responses to microinjection of glycine (1.0 M, 60 nl) into the PRF before and after injection of the synaptic blocking agent cobalt chloride (4.0 mM, 200 nl) into the RVLM. Glycine injections into the PRF caused decreases in arterial pressure, heart rate, and discharge of renal sympathetic nerves. Synaptic blockade of the RVLM almost eliminated cardiovascular and sympathetic responses to glycine injections into the PRF and blocked somatosympathetic reflexes in the renal nerve. Cobalt injections into the RVLM had very small effects on basal renal nerve firing, arterial pressure, or heart rate. These results suggest that the neurons within the RVLM relay influences from the PRF to sympathetic preganglionic neurons. Because injections of the excitatory amino acid antagonist, kynurenate, into the RVLM also interrupted responses to blockade of the PRF and blocked somatosympathetic reflexes, glutamate is a likely neurotransmitter from the PRF to the RVLM and for somatosympathetic reflexes.

Dorsal root afferent influences on tonic firing of renal and mesenteric sympathetic nerves in rats

After spinal cord transection in cats and rats, the activity of many sympathetic nerves is not entirely lost, and firing of other nerves continues unabated or is increased. This study was done to evaluate the importance of dorsal root afferent discharge on the generation of tonic sympathetic activity in renal and mesenteric postganglionic nerves in spinal rats and in rats with intact neuraxes. Sympathetic discharge was recorded in anesthetized rats, and peripheral afferent influences were eliminated by dorsal rhizotomy from T4 to L2. Activity of renal and mesenteric nerves was well maintained after high cervical and thoracic (T4) cord transections. Rhizotomy had no effect on sympathetic discharge in rats with intact neuraxes but decreased renal nerve activity significantly (-25%) in spinal rats. Because rhizotomy decreased mesenteric discharge in only three of six spinal rats, mean mesenteric nerve discharge was not decreased significantly. The decreased renal nerve discharge after dorsal rhizotomy could not be attributed to input from any specific spinal segment, and ipsilateral input was no greater than contralateral input. After rhizotomy, both renal and mesenteric nerves had substantial excitatory drive from the transected, deafferented spinal cord. These findings demonstrate that dorsal root afferent influences on spinal neurons can contribute to the generation of tonic discharge in some sympathetic nerves in spinal animals.

Cardiovascular effects of central administration of cholinomimetics in anesthetized cats

The cardiovascular effects of central administration of cholinomimetics were investigated in anesthetized cats, to identify the site and mechanism of their action. Physostigmine, 10–100 μg, given by intracerebroventricular administration (i.c.v.) caused a dose-dependent reduction in blood pressure and renal sympathetic nerve discharges and no change in heart rate, which were antagonized by intravenous injection (i.v.) of atropine but not by methscopolamine or pirenzepine, given intravenously. Carbachol 3–30 μg (i.c.v.) reduced blood pressure and renal sympathetic nerve discharges and caused no change in heart rate. The M 1 muscarinic agonist, McN-A-343, 100–1000 μg (i.c.v.) did not affect blood pressure, heart rate or renal sympathetic nerve discharges. Bilateral application of physostigmine, 10–100 μg/site on the ventral medullary surface, decreased blood pressure and renal sympathetic nerve discharges but not heart rate. Carbachol, 3–30 μg/site, caused reductions in blood pressure and renal symphathetic nerve discharges and no change in heart rate. Atropine, but not pirenzepine or methscopolamine, reversed the effects of physostigmine or carbachol. Treatment with McN-A-343, 100–1000 μg/site, did not alter blood pressure, heart rate or renal sympathetic nerve discharges. Under pretreatment with atropine into the ventral medulla but not pirenzepine, physostigmine, given intravenously, did not influence blood pressure. It is concluded that a cholinergic mechanism, concerned with a depressor response, is located on the ventral medulla. Muscarinic receptors of the non-M 1 subtype, possibly M 2, are related to this mechanism.

Areas of rostral medulla providing tonic control of renal and splenic nerves

The objective of this study was to determine whether nonuniform control of tonic discharge of renal and splenic nerves by the rostral ventrolateral medulla (RVLM) is dependent on viscerotopic representation of the kidney and the spleen in this region. Small (15 nl, 13 pmol) injections of the potent tau-aminobutyric acid agonist muscimol were used to map the RVLM of anesthetized rats, searching for areas that selectively provided tonic excitation of renal or splenic nerves. Most of the muscimol microinjections produced depressor responses and inhibition of sympathetic nerve activity. Activity of renal nerves was inhibited significantly more than that of splenic nerves, but we found no evidence for topographical organization of RVLM influences on tonic activity of these two nerves. However, this investigation did yield an important new observation, since approximately 10% of the injections caused pressor responses and increases in sympathetic discharge. The unexpected increases must have been caused by blockade of small groups of tonically active sympathoinhibitory neurons located throughout the RVLM. This disinhibition was not evoked from any specific region of the RVLM. In conclusion, the RVLM neurons and putative interneurons that tonically control the discharge of postganglionic renal and splenic neurons appear to be distributed homogeneously throughout this area. Neither excitatory nor inhibitory elements were organized topographically to specifically influence the renal or the splenic nerve. The neural organization responsible for the preferential effect on renal nerves may exist in the local microcircuitry within the RVLM and will be revealed only by an even more discrete analysis of these circuits.

Evidence for descending tonic inhibition specifically affecting sympathetic pathways to the kidney in rats.

1. The present study investigated the possibility that pre- and postganglionic neurones innervating the kidney and spleen in rats are affected by descending inhibitory as well as descending excitatory influences. This hypothesis was tested by comparing the effects of cervical spinal cord transection to the effects of blockade of tonic activity of excitatory neurones in the rostral ventrolateral medulla (RVLM). 2. Electrical discharge of multifibre postganglionic renal and splenic and preganglionic greater splanchnic nerves and 13th thoracic (T13) white rami was recorded in artificially respired, urethane-anaesthetized rats. In one group of rats, descending supraspinal pathways were interrupted by cervical spinal cord transection. In another group, tonic activity of rostral ventrolateral medulla (RVLM) neurones was blocked by bilateral microinjections of the inhibitory amino acid glycine. The effects of spinal cord transection were compared to effects of this bilateral RVLM blockade and to effects of unilateral RVLM blockade described in a previous study. 3. Spinal cord transection caused decreases in preganglionic greater splanchnic and postganglionic splenic nerves which were of the same magnitude as those caused by bilateral blockade of the RVLM. 4. In contrast, discharge of renal nerves was decreased more by bilateral RVLM blockade than by cervical spinal cord transection. Similarly, even unilateral RVLM blockade caused greater decreases in discharge of T13 white rami than were caused by spinal cord transection. 5. These findings suggest that renal nerves and their preganglionic inputs (T13 white rami) are controlled in part by tonic sympathoinhibitory influences which can be unmasked by blockade of the RVLM. These sympathoinhibitory influences do not appear to affect the activity of splanchnic and splenic nerves.

Effects of spinal cord transection on sympathetic discharge in decerebrate-unanesthetized cats.

Previous experiments in our laboratory have shown that discharge of splenic, mesenteric, and splanchnic nerves is well maintained after spinal cord transection in chloralose-anesthetized cats (8, 9, 11). The primary purpose of this investigation was to determine if maintained sympathetic discharge could be observed after spinal transection in the absence of chloralose anesthesia. In cats anesthetized with alphaxalone-alphadolone, changes in splanchnic discharge, blood pressure, and heart rate caused by decerebration and removal of the forebrain were observed. This procedure decreased blood pressure, increased heart rate, and had no immediate effect on sympathetic discharge or its rhythm (assessed by power density spectral analysis). One hour after decerebration and termination of anesthesia, splanchnic discharge had increased by approximately 36%. Next, effects of spinal cord transection on discharge of splanchnic, mesenteric, and renal nerves were observed in the decerebrate-unanesthetized cats. Splanchnic discharge decreased by 50%, mesenteric nerve discharge was unchanged, and renal nerve discharge decreased by 97%. Therefore, splanchnic nerve discharge was not as well maintained in decerebrate-unanesthetized cats as it had been in chloralose-anesthetized animals, and the remaining splanchnic discharge appeared to affect mesenteric nerves preferentially. Finally, spectral analysis of the splanchnic discharge demonstrated that before cord transection, most of the signal was in the 0- to 6-Hz frequency range, whereas after transection the proportion of signal in this frequency range was significantly reduced and the proportion in higher frequencies (7-25 Hz) was significantly increased. This loss of low-frequency rhythmicity is consistent with findings in our previous studies in chloralose-anesthetized cats.

Abnormalities of sympathetic vasomotor tone in distal axonal neuropathy

Microneurographic studies have shown that sympathetic vasomotor nerve activity is observed less frequently in patients with peripheral neuropathy than in controls, but when detected its pattern and the baroreflex latencies appear to be normal. Vasomotor nerve function was examined in chloralose-urethane anaesthetised dogs by comparing the discharge of renal sympathetic nerves in control animals and animals with acrylamide neuropathy. There was a normal pattern of pulse related inhibition of sympathetic nerve activity as well as normal amplitude spontaneous compound nerve action potentials in the animals with neuropathy. When vasomotor tone was altered abruptly by raising pressure in a bilateral isolated carotid sinus preparation, the baroreflex latencies were normal in the affected animals. However, when carotid sinus pressure was kept constant, pulse-related sympathetic inhibition, normally mediated by vagal cardiopulmonary baroreceptors, was absent in animals with neuropathy. It is likely that the vagal nerve fibres to cardiopulmonary baroreceptors as well as the receptors themselves are damaged while shorter carotid sinus nerve fibres are relatively spared in axonal neuropathies. As long as these shorter nerves are intact patients with axonal neuropathy should have relatively normal baroreflexes and normal sympathetic vasomotor tone when measured microneurographically.