Baroreflex control of renal sympathetic nerve activity and heart rate in near-term fetal sheep

Late preterm infants, born between 34 and 36 weeks gestation, have significantly higher morbidity than neonates born at full term, which may be partly related to reduced sensitivity of the arterial baroreflex. The present study assessed baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) in near-term fetal sheep at 123 ± 1 days gestation. At this age, although fetuses are not fully mature in some respects (term is 147 days), sleep-state cycling is established [between high-voltage, low-frequency (HV) and low-voltage, high-frequency (LV) sleep], and neural myelination is similar to the term human infant. Fetal sheep were instrumented to record blood pressure (BP), HR (n = 15) and RSNA (n = 5). Blood pressure was manipulated using vasoactive drugs, phenylephrine and sodium nitroprusside. In both HV and LV sleep, phenylephrine was associated with increased arterial BP and decreased HR. In HV sleep, phenylephrine was associated with a fall in RSNA, from 124 ± 14 to 58 ± 11% (P < 0.05), but no significant change in RSNA in LV sleep. In contrast, the fall in BP after sodium nitroprusside was associated with a significant increase in HR during LV but not HV sleep, and there was no significant effect of hypotension on RSNA. These data demonstrate that in near-term fetal sheep baroreflex activity is only partly active and is highly modulated by sleep state. Critically, there was no RSNA response to marked hypotension; this finding has implications for the ability of the late preterm fetus to adapt to low BP.     

20-HETE increases renal sympathetic nerve activity via activation of chemically and mechanically sensitive muscle afferents

Arachidonic acid and its metabolites produced via cyclooxygenase (COX) and lipoxygenase pathways have been reported to contribute to the cardiovascular reflexes evoked by stimulating thin fibre muscle afferents during muscle contraction. 20-Hydroxyeicosatetraenoic acid (20-HETE), a primarily metabolized product of arachidonic acid by cytochrome P450 enzymes, can be accumulated in contracting muscles. Thus, the purpose of this study was to determine the role of 20-HETE in modulating the reflex sympathetic responses to activation of chemically and mechanically sensitive muscle afferents. The renal sympathetic nerve activity (RSNA) and cardiovascular responses were examined after injections of 20-HETE into the arterial blood supply of the hindlimb muscles of decerebrated rats. This induced a dose-dependent increases in RSNA and mean arterial pressure (MAP). We also tested the hypothesis that 20-HETE would sensitize muscle afferents and, thereby, augment the RSNA and blood pressure response to muscle stretch. The results show that arterial infusion of 20-HETE significantly enhanced the RSNA and MAP responses to muscle stretch. In contrast, N -hydroxy- N '-(4-butyl-2-methylphenyl)formamidine, a potent inhibitor of 20-HETE production, attenuated the reflex muscle responses. Furthermore, the sensitizing effect of 20-HETE on the muscle reflex was significantly attenuated after blocking COX activity with indomethacin. Our data suggest that 20-HETE plays a role in modulating muscle afferent-mediated sympathetic responses, probably through engagement of a COX-dependent mechanism.     

Baroreflex mechanisms regulating the occurrence of neural spikes in human muscle sympathetic nerve activity

This study tested the hypothesis that the discharge patterns of action potentials (APs) within bursts of postganglionic muscle sympathetic nerve activity (MSNA) are subject to arterial baroreflex control but in a manner that varies inversely with AP size. MSNA data were collected over 5 min of supine rest in 15 young and healthy individuals (8 males; 24 ± 4 yr of age; means ± SD). The baroreflex threshold and sensitivity diagrams were constructed for both the integrated sympathetic bursts and for the AP clusters. For the integrated bursts, a strong linear relationship between burst probability and diastolic blood pressure (DBP) was observed (P < 0.05). There was little relationship between integrated burst strength (amplitude) and DBP. On average, 12 AP clusters were observed across individuals. Larger APs tended to appear in the larger bursts. Linear regression analysis was used to study the baroreflex threshold (probability of AP cluster occurrence vs. DBP) as well as the baroreflex sensitivity (AP cluster size vs. DBP). A significant reflex threshold relationship was observed in 75-100% of AP clusters across all individuals. In contrast, significant reflex sensitivity relationships were observed in only 9 of 15 individuals and for limited APs. Overall, the slope of the AP baroreflex threshold relationship was greater for the small-medium sized AP clusters than that of the larger APs. Therefore, within each burst, the small-medium sized APs are governed by the baroreflex mechanism. However, the large APs, which tend to appear in the large integrated bursts, are weakly associated with a baroreflex control feature. The variable impact of baroreflex control over AP occurrence provides a plausible explanation for the overall weak baroreflex control over integrated burst strength, a feature that is determined by both the number and size of the AP complement.     

Consistent interindividual increases or decreases in muscle sympathetic nerve activity during experimental muscle pain

We recently showed that long-lasting muscle pain, induced by intramuscular infusion of hypertonic saline, evoked two patterns of cardiovascular responses across subjects: one group showed parallel increases in muscle sympathetic nerve activity (MSNA), blood pressure, and heart rate, while the other group showed parallel decreases. Given that MSNA is consistent day to day, we tested the hypothesis that individuals who show increases in MSNA during experimental muscle pain will show consistent responses over time. MSNA was recorded from the peroneal nerve, together with blood pressure and heart rate, during an intramuscular infusion of hypertonic saline causing pain for an hour in 15 subjects on two occasions, 2–27 weeks apart. Pain intensity ratings were not significantly different between the first (5.8 ± 0.4/10) and second (6.1 ± 0.2) recording sessions. While four subjects showed significant decreases in the first session (46.6 ± 9.2 % of baseline) and significant increases in the second (159.6 ± 8.9 %), in 11 subjects, there was consistency in the changes in MSNA over time: either a sustained decrease (55.6 ± 6.8 %, n = 6) or a sustained increase (143.5 ± 6.1 %, n = 5) occurred in both recording sessions. There were no differences in pain ratings between sessions for any subjects. We conclude that the changes in MSNA during long-lasting muscle pain are consistent over time in the majority of individuals, reflecting the importance of studying interindividual differences in physiology.     

Weakened long-range correlation of renal sympathetic nerve activity in Wistar rats after anaesthesia

In this study we employed multiscale entropy (MSE) measurement to assess the long-range temporal correlation (LRTC) of multifibre renal sympathetic nerve activity (RSNA) signals in conscious and anaesthetized Wistar rats. It was found that both groups presented more complex MSE profiles than an uncorrelated process. Moreover, the results of MSE analysis of RSNA demonstrated that the entropy values, derived from the conscious group, increased on small time scales and then stabilized to a relatively constant value, however, the entropy measure, derived from animals with anaesthesia, almost monotonically decreased. The present study shows that while LRTC in the temporal dynamics of energy fluctuations of RSNA does not implicate a unique mechanism, the data for the first time provide evidence of much less temporal correlation in anaesthetized condition. This suggests the fractal properties of underlying dynamical system have been effectively eliminated by anaesthesia. These results demonstrate that apparently random fluctuations in multifibre RSNA are dictated by a complex deterministic process that imparts "long-term" memory to the dynamic system. However, this memory is significantly weakened by anaesthesia.     

Baroreflex modulation of sympathetic activity and sympathetic neurotransmitters in humans

We raised and lowered arterial pressures with stepwise intravenous infusions of phenylephrine and nitroprusside in ten healthy young men and measured changes of R-R intervals, post-ganglionic peroneal nerve muscle sympathetic activity, and antecubital vein plasma noradrenaline and neuropeptide Y concentrations. Respiratory peak-valley R-R interval changes declined with arterial pressure reductions, but did not rise with pressure elevations. Sympathetic activity was modulated by respiration over the entire range of pressures and, at each pressure, was more prominent in expiration than inspiration. Levels of muscle sympathetic nerve activity were low during supine rest, were suppressed almost completely during small increases of pressure, and were increased proportionally during pressure reductions. Over a range of average diastolic pressures from 69 to 89 mmHg, antecubital vein plasma noradrenaline levels were related linearly (r = 0.86, P = 0.0001) to muscle sympathetic nerve activity. Neuropeptide Y levels increased proportionally with muscle sympathetic nerve activity during pressure reductions, but did not decline during pressure elevations. Our results suggest that in man, muscle sympathetic outflow is modulated finely by small changes of baroreceptor input, and that during pharmacologically induced changes of arterial pressure, changes of antecubital vein plasma noradrenaline concentrations provide excellent estimates of changes of sympathetic nerve traffic to skeletal muscle.     

Baroreflex and somato-reflex control of blood pressure, heart rate and renal sympathetic nerve activity in the obese Zucker rat

It has been reported that the baroreflex control of heart rate (HR) and sympathetic nerve activity (SNA) is attenuated in obese Zucker rats (OZRs) compared with age-matched lean animals (LZRs). What is not known, however, is the extent to which the baroreflex control of mean arterial blood pressure (MAP) is altered in the OZR. In addition, it is not known whether the interactions of other sensory nerve inputs on autonomic control are altered in the OZR compared with the LZR. The aim of this study was to determine the baroreflex control of MAP, HR and renal SNA (RSNA) in the OZR and LZR using an open-loop baroreflex approach. In addition, the effect of brachial nerve stimulation (BNS) on the baroreflex control was determined in these animals. Age-matched, male LZRs and OZRs were anaesthetized, and the carotid baroreceptors were vascularly isolated, bilaterally. The carotid sinus pressure was increased in 20 mmHg increments from 60 to 180 mmHg using an oscillating pressure stimulus. Baroreflex function curves were constructed using a four-parameter logistic equation, and gain was calculated from the first derivative, which gave a measure of baroreceptor sensitivity, before and during BNS. The range over which the baroreflex could change MAP (28 ± 6 versus 87 ± 5 mmHg; mean ± SEM), HR (17 ± 4 versus 62 ± 11 beats min(-1)) and normalized RSNA (NormNA; 22 ± 4 versus 76 ± 11%) was significantly decreased in the OZR compared with the LZR. Likewise, the maximal gain was lower in the OZR, as follows: MAP -0.88 ± 0.22 versus -2.26 ± 0.17; HR -0.42 ± 0.18 versus -1.44 ± 0.22 beats min(-1); and NormNA -0.54 ± 0.14 versus -1.65 ± 0.30% mmHg(-1). There was no difference in the mid-point of the baroreflex curve for each variable between the OZR and LZR. However, the minimal values obtained when the baroreceptors were maximally loaded were higher in the OZR (MAP 68 ± 5 versus 53 ± 4 mmHg; HR 455 ± 7 versus 390 ± 13 beats min(-1); and NormNA -19 ± 4 versus -48 ± 8%). Brachial nerve stimulation in the LZR resulted in an upward and rightward resetting of the baroreflex control of MAP and RSNA, and abolished baroreflex control of HR. The baroreflex control of RSNA in the OZR during BNS was further attenuated and reset upwards and to the right, while the HR response was abolished. With respect to MAP, the baroreflex curve reset upwards and to the right to a point comparable with the LZR during BNS. These data show that there is an attenuated baroreflex control in the OZR and that the ability to reset to higher arterial pressure during somatic afferent nerve stimulation is similar to that in the LZR.     

Arousal increases baroreflex inhibition of muscle sympathetic activity

AIM: Surprising sensory stimuli causing arousal are known to evoke short-lasting activation of human sympathetic activity in skin but not in muscle nerves. In fact, anecdotal observations suggest that muscle sympathetic activity may be inhibited. To test this hypothesis, the effects of surprising somatosensory (electrical skin pulses) or visual (flash) stimuli on multiunit muscle sympathetic activity were studied in 36 healthy subjects, aged 19-71 years. METHODS: The stimuli were given either 200 or 400 ms after the R-wave of the electrocardiogram. Dummy stimuli, consisting of trigger pulses without sensory stimuli, served as controls. RESULTS: On a group basis, a single sensory stimulus of either type attenuated the amplitude of one or two sympathetic bursts, while no such effects occurred after dummy stimuli. Individually, the inhibition was evoked by at least one stimulus modality or delay in 16 subjects, whereas in three subjects no significant inhibition occurred. Electrodermal signs of skin sympathetic activation were present in all subjects. Compared with one, five repeated electrical skin pulses induced only minor additional inhibition of muscle sympathetic activity, indicating marked habituation of the neural response. In nine subjects, the experiments were repeated once and in three subjects twice (with intervals of 2-3 months); in 11 of the 12 subjects, the sympathetic effects were reproducible. In the group of subjects without significant sympathetic inhibition the stimuli induced a small, transient increase of mean blood pressure, which was not present in the group with sympathetic inhibition. CONCLUSION: The finding that different sensory stimuli induce similar effects that habituate markedly on repetition suggests that the inhibition of muscle sympathetic activity is because of arousal. The interindividual differences in sympathetic and blood pressure effects may be part of interindividual differences in behavioural responses to stress.     

Responses of muscle sympathetic nerve activity and cardiac output to the cold pressor test.

We measured muscle sympathetic nerve activity (MSA) to clarify the mechanisms of the blood pressure rise during cold pressor test (CPT), simultaneously with impedance cardiography and blood pressure wave measurement in 10 healthy subjects. MSA remained unchanged during the initial period of 0-30s of the CPT and increased remarkably during the later period of 30-90s of the CPT, while cardiac output exhibited a slight increase during the initial period but not during the later period. Mean blood pressure increased significantly throughout the entire period of CPT and reached the maximal level during 90-120s of the CPT. The mean blood pressure and total peripheral resistance during the CPT showed a linear correlation with MSA. In conclusion, an increase of cardiac output elevates blood pressure at the initial period of the CPT with little increase in MSA, while an increase of MSA plays an essential role to elevate the blood pressure at the later period of the CPT.     

Baroreflex “resetting” by arterial hypoxia in the renal and cardiac sympathetic nerves of the rabbit

1. Renal and cardiac sympathetic baroreflex functions were studied in sodium pentobarbitone anaesthetized rabbits given succinylcholine, during constant artificial ventilation with air and with hypoxic gas mixtures. Mean arterial pressure (MAP) was raised and lowered between values of 40 and 140 mm Hg by means of aortic and vena caval periovascular balloons and integrated sympathetic nerve activity (SNA) was recordered. 2. The relationship between MAP and SNA was sigmoid, with upper and lower plateau levels. The curves were defined by calculating median blood pressure, SNA Range and reflex gain. In both renal and cardiac sympathetics section of the carotid sinus and aortic nerves completely abolished the MAP-related changes in SNA. 3. The renal baroreflex curves were reset from control levels during hypoxia. Median blood pressure increased, as did SNA Range and gain. These effects were due to central interactions between arterial baroreceptor, arterial chemoreceptor and vagal afferent activity. 4. The cardiac sympathetic baroreflex curves were shifted in the opposite direction from control with reduction in median blood pressure, SNA Range and reflex gain. These changes were due to chemoreceptor-arterial baroreceptor interactions. 5. Arterial hypoxia thus evokes a differentiated pattern of baroreflex resetting in the renal and cardiac sympathetic montoneuron pools with differing changes in neural response range and sensitivity to arterial pressure changes.     

Cardiopulmonary sympathetic afferent influences on renal nerve activity.

Cardiopulmonary sympathetic afferent nerves may affect renal control of intravascular volume by influencing renal sympathetic nerve activity. This influence was evaluated in alpha-chloralose anesthetized, vagotomized, sino-aortic denervated cats. When the afferent nerves were activated with a single electrical stimulus, the renal nerve responded with an excitatory burst of activity followed by a long period of inhibition. This response had characteristics of a supraspinal reflex. Repetitive stimulation of the sympathetic afferent nerve either inhibited or excited renal nerves and increased or decreased systemic blood pressure. The direction of these changes depended on stimulus parameters. No obligatory correlation in the direction of change of nerve activity and blood pressure was observed. Activation of cardiopulmonary sympathetic afferent nerves by intravascular volume expansion inhibited renal nerve discharge. Inhibition was elminated by sectioning the sympathetic afferent nerves. Volume expansion had no effect on lumbar sympathetic discharge monitored simultaneously with renal nerve activity. This observation suggests specificity of reflex influences of these afferent nerves on the kidney. In conclusion, cardiopulmonary sympathetic afferent nerves can reflexly alter renal nerve activity, and therefore may affect renal control of intravascular volume.     

Acute adenosine increases cardiac vagal and reduces sympathetic efferent nerve activities in rats

Adenosine is the first drug of choice in the treatment of supraventricular arrhythmias. While the effects of adenosine on sympathetic nerve activity (SNA) have been investigated, no information is available on the effects on cardiac vagal nerve activity (VNA). We assessed in rats the responses of cardiac VNA, SNA and cardiovascular variables to intravenous bolus administration of adenosine. In 34 urethane-anaesthetized rats, cardiac VNA or cervical preganglionic sympathetic fibres were recorded together with ECG, arterial pressure and ventilation, before and after administration of three doses of adenosine (100, 500 and 1000 μg kg(-1)). The effects of adenosine were also assessed in isolated perfused hearts (n = 5). Adenosine induced marked bradycardia and hypotension, associated with a significant dose-dependent increase in VNA (+204 ± 56%, P < 0.01; +275 ± 120%, P < 0.01; and +372 ± 78%, P < 0.01, for the three doses, respectively; n = 7). Muscarinic blockade by atropine (5 mg kg(-1), i.v.) significantly blunted the adenosine-induced bradycardia (-56.0 ± 4.5%, P < 0.05; -86.2 ± 10.5%, P < 0.01; and -34.3 ± 9.7%, P < 0.01, respectively). Likewise, adenosine-induced bradycardia was markedly less in isolated heart preparations. Previous barodenervation did not modify the effects of adenosine on VNA. On the SNA side, adenosine administration was associated with a dose-dependent biphasic response, including overactivation in the first few seconds followed by a later profound SNA reduction. Earliest sympathetic activation was abolished by barodenervation, while subsequent sympathetic withdrawal was affected neither by baro- nor by chemodenervation. This is the first demonstration that acute adenosine is able to activate cardiac VNA, possibly through a central action. This increase in vagal outflow could make an important contribution to the antiarrhythmic action of this substance.     

The effect of chemoreceptor stimulation upon muscle sympathetic nerve activity

The aim of this investigation was to quantify the combined peripheral and central chemoreceptor contribution to sympathetic outflow above (post) and below (pre) the chemoreceptor ventilatory threshold (CVT). We measured muscle sympathetic nerve activity (MSNA) in seven subjects during hypoxic/hypercapnic and room air rebreathe protocols. Comparisons were made using a repeated measures analysis of variance with two within subject factors. One factor contained three levels—hyperventilation, pre-CVT, and post-CVT. The other factor contained two levels—rebreathe and control. Total MSNA increased from hyperventilation to pre-CVT to post-CVT in the rebreathe trial (385.7 ± 95.9, 592.4 ± 155.7, 882.0 ± 235.4 au/15 s respectively) and remained constant in the control trial (433.0 ± 189.3, 409.1 ± 183.4, 406.1 ± 161.4 au/15 s respectively). Ventilation increased in the rebreathe trial only. Heart rate and blood pressure did not change in either trial. These data suggest that the chemoreceptors significantly contribute to the modulation of sympathetic outflow.     

Impact of cardiac hypertrophy on arterial and cardiopulmonary baroreflex control of renal sympathetic nerve activity in anaesthetized rats

This study aimed to quantify the effect of cardiac hypertrophy induced with isoprenaline and caffeine on reflex regulation of renal sympathetic nerve activity by the arterial and cardiopulmonary baroreceptors. Male Wistar rats, untreated or given water containing caffeine and subcutaneous (s.c.) isoprenaline every 72 h for 2 weeks or thyroxine s.c. for 7 days, were anaesthetized and prepared for measurement of renal sympathetic nerve activity or cardiac indices. Both isoprenaline-caffeine and thyroxine treatment blunted weight gain but increased heart weight and heart weight to body weight ratio by 40 and 14% (both P < 0.01), respectively. In the isoprenaline-caffeine group, the maximal rate of change of left ventricular pressure and the contractility index were higher by 17 and 14% (both P < 0.01), respectively, compared with untreated rats. In the isoprenaline-caffeine-treated rats, baroreflex gain curve sensitivity was depressed by approximately 30% (P < 0/05), while the mid-point blood pressure was lower, by 15% (P < 0/05), and the range of the curve was 60% (P < 0.05) greater than in the untreated rats. An acute intravenous infusion of a saline load decreased renal sympathetic nerve activity by 42% (P < 0.05) in the untreated rats but had no effect in the isoprenaline-caffeine- or the thyroxine-treated groups. The isoprenaline-caffeine treatment induced cardiac hypertrophy with raised cardiac performance and an associated depression in the reflex regulation of renal sympathetic nerve activity by both high- and low-pressure baroreceptors. The thyroxine-induced cardiac hypertrophy also blunted the low-pressure baroreceptor-mediated renal sympatho-inhibition. These findings demonstrate that in cardiac hypertrophy without impaired cardiac function, there is a blunted baroreceptor control of renal sympathetic outflow.     

Impaired baroreflex control of renal sympathetic nerve activity in type 1 diabetic mice (OVE26)

To investigate the effects of chronic diabetes on baroreflex control of renal sympathetic nerve activity (RSNA), OVE26 diabetic (transgenic mouse line which develops hyperglycemia within the first 3 weeks after birth) and FVB control mice 5–6 months old were studied. Under anesthesia, RSNA in response to sodium nitroprusside (SNP)– and phenylephrine (PE)-induced mean arterial pressure changes (ΔMAP) were measured. Baroreflex-induced inhibition of RSNA during PE infusion was characterized using the sigmoid logistic function curve. Baroreflex-induced excitation of RSNA during SNP infusion was characterized by the RSNA vs. ΔMAP relationship. Mean arterial pressure (MAP) responses to the left aortic depressor nerve (ADN) stimulation were evaluated. Compared to FVB control, we found in OVE26 mice that (1) RSNA in response to MAP increase during PE infusion was dramatically reduced, as characterized by the maximal gain of the RSNA sigmoid logistic function curve (FVB: −20.0±5.1; OVE26: −7.6±0.8%/mm Hg, P<0.05); (2) RSNA in response to MAP decrease during SNP infusion was also attenuated (P<0.05); (3) MAP responses to ADN stimulation were reduced (P<0.05). We concluded that chronic diabetes impairs baroreflex control of RSNA in OVE26 diabetic mice. The use of the transgenic OVE26 diabetic mouse model may underlie a foundation for the further understanding of diabetes-induced autonomic neuropathy.     

The variability of muscle nerve sympathetic activity in resting recumbent man

1. Pulse synchronous bursts of multi-unit sympathetic activity was recorded from median or peroneal muscle nerve fascicles in fourteen subjects resting in the recumbent position. The neural activity was quantitated in terms of burst incidence, i.e. the number of bursts in the mean voltage neurogram/100 heart beats, during successive rest periods of 2-4 min.2. For each individual the burst incidence was fairly constant between different rest periods but the mean burst incidence varied widely between individuals, the range being from less than 10 to more than 90 bursts/100 heart beats.3. Simultaneous double nerve recordings were made on one subject from median and peroneal nerves and on eight subjects from the two peroneal nerves. There was always close similarity between the two records in such experiments regardless of which muscles the nerve fascicles innervated. When analysed separately the difference in burst incidence between the two sides ranged from 0.7 to 5.1 bursts/100 heart beats. The findings suggest that sympathetic neurones destined to skeletal muscles are subjected to a homogenous central drive and that contributions to the activity from ganglionic or segmental sources are of lesser importance.4. On seven subjects repeated recordings at rest were made with intervals of 3 weeks-21 months between recordings. In each subject mean burst incidences were similar in all recordings (range of differences 0.5-11.2 bursts/100 heart beats) suggesting an individually constant level of sympathetic activity in muscle nerves.5. For each individual the variability of burst amplitudes in the mean voltage neurogram was described by burst amplitude spectra. Most subjects had a relatively larger proportion of small than high amplitude bursts, but there was a tendency for more even amplitude distributions in subjects with high burst incidence. The finding may be an indication of interindividual differences in the average number of impulses/burst.6. It is concluded that the multi-unit recording technique can be used for comparisons of the level of muscle nerve ;sympathetic tone' between different subjects.     

Intravascular mechanoreceptor modulation of renal sympathetic nerve activity in the cat

Experiments were performed in chloralose-anesthetized cats to characterize intravascular mechanoreceptro input to renal nerve activity in the intact and vagotomized sinoaortic-denervated states. High-pressure intravascular mechanoreceptors were stimulated by rises in arterial pressure caused by norepinephrine. Low-pressure intravascular mechanoreceptors were stimulated by progressive blood volume expansion (14-23%) at a rate of 4.4 or 17.6 ml/min. In addition, veratrine was used to stimulate directly both high- and low-pressure receptors. In the intact animal the administration of norepinephrine or blood volume expansion was associated with substantial decreases in renal nerve activity. Veratrine also caused a large dose-related decrease in renal nerve activity. However, in the vagotomized sinoaortic-denervated animal there was no change in renal nerve activity with norepinephrine, volume expansion, or veratrine administration. These experiments demonstrate that the major afferent pathways for renal sympathetic circulatory reflexes are confined to the carotid sinus and aortic and vagus nerves. No evidence was found for a significant contribution from sympathetic afferent nerves.