Lumbar Sympathetic Nerve Activity Research Articles

Sympathetic nerve responses to muscle contraction and stretch

The aim of this study was to examine differential sympathetic nerve responses in peripheral tissues during exercise. In decerebrate rats, we examined renal and lumbar (which innervates hindlimb) sympathetic nerve activities (RSNA and LSNA, respectively) during: 1-min rhythmic (1- to 4-s stimulation-to-relaxation) contraction of the triceps surae muscles; rhythmic stretch; and rhythmic contraction with hindlimb ischemia. During these interventions, the RSNA and LSNA responded synchronously as tension was developed. In both rhythmic contraction (n=10, +465±40 g in tension) and muscle stretch (n=10, +506±36 g), the RSNA response was significantly greater than the LSNA response (+109±19 vs. +75±11% P<0.05 in contraction and +99±16 vs. +55±11% P<0.05 in stretch from baseline). Hindlimb ischemia (n=7) enhanced both the RSNA and LSNA responses to contraction by 18% and 33% (P<0.05), respectively. The data demonstrate that the RSNA responses to muscle stretch and contraction are greater than those seen with LSNA. We suggest that the differential sympathetic outflow induced by the muscle afferents activation contributes to the distribution of cardiac output observed during exercise. Moreover, ischemic metabolites produced in contracting muscle likely sensitizes the muscle afferents engaged by contraction and stretch. Supported by NIH R01 HL075533 (JL) and R01 HL078866 (JL) and R01 HL060800 (LIS).

Glutamatergic Inputs in the Hypothalamic Paraventricular Nucleus Maintain Sympathetic Vasomotor Tone in Hypertension

The paraventricular nucleus (PVN) of the hypothalamus is critical to the regulation of sympathetic output. The PVN hyperactivity is known to cause increased sympathetic nerve activity in spontaneously hypertensive rats (SHRs). The purpose of this study was to determine whether glutamatergic input to the PVN contributes to heightened sympathetic outflow in hypertension. Lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate were recorded from anesthetized SHRs and Wistar-Kyoto (WKY) rats. Bilateral microinjection of an N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonopentanoic acid, or a non-N-methyl-D-aspartate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, into the PVN dose-dependently decreased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in SHRs but not in WKY rats. Bilateral microinjection of kynurenic acid into the PVN also significantly decreased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in SHRs but not in WKY rats. Furthermore, microinjection of gabazine, a specific GABA(A) receptor antagonist, into the PVN increased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in both SHRs and WKY rats. Notably, this response was significantly attenuated in SHRs compared with that in WKY rats. In addition, kynurenic acid abolished the sympathoexcitatory and pressor responses to microinjection of gabazine into the PVN in both SHRs and WKY rats. Thus, this study provides new functional evidence that resting sympathetic vasomotor tone is maintained by tonic glutamatergic input in the PVN in SHRs. Removal of GABAergic inhibition results in augmented glutamatergic input in the PVN, which probably constitutes an important source of excitatory drive to the brain stem vasomotor neurons in hypertension.

Dietary salt loading exacerbates the increase in sympathetic nerve activity caused by intravenous insulin infusion in rats

Obesity and type 2 diabetes mellitus frequently produce chronic elevations in blood insulin levels. Importantly, hyperinsulinemia stimulates increases in sympathetic nerve activity that may predispose to hypertension, atherosclerosis, and end-organ damage. Because depletion of dietary salt (NaCl) increases angiotensin II levels, which has been shown to enhance sympathetic responses to excitatory stimuli such as thermal stimulation and bicuculline in the hypothalamus, we predicted that insulin-induced elevations in lumbar sympathetic activity would be augmented by low NaCl and suppressed by high dietary NaCl. Adult male Sprague-Dawley rats were randomized into groups receiving low (0.0 mEq/d, n = 10), normal (2.0 mEq/d, n = 10), and high (5.7 mEq/d, n = 10) NaCl for a period of 8 days. After this, the animals were anesthetized for measurement of heart rate, mean arterial pressure, and lumbar sympathetic nerve activity during 110 minutes of intravenous insulin infusion (15 mU/kg per minute) with euglycemic clamp. Insulin administration caused modest blood pressure decreases accompanied by heart rate increases that were similar across the 3 dietary groups. Unexpectedly, sympathetic increases to insulin were lowest in the low-NaCl group (100%-135% ± 24%), moderate in the normal-NaCl group (100%-170% ± 23%), and greatest in the high-NaCl group (100%-252% ± 39%). Dietary NaCl level did not affect baseline blood glucose or insulin sensitivity as assessed by euglycemic clamp. These findings indicate that dietary salt loading exacerbates the lumbar sympathoexcitatory response to intravenous insulin infusion in rats.

Differential response of renal and lumbar sympathetic nerve activity during freezing behaviour in conscious rats

Stressful or threatening sensory stimulation results in decreased motor activity in some species, a response referred to as “freezing” behaviour. The present study was designed to examine sympathetic and hemodynamic responses during freezing behaviour induced by 90 dB noise exposure in conscious rats. Wistar male rats were instrumented chronically with electrodes for measurements of renal (RSNA) and lumbar (LSNA) sympathetic nerve activity, electroencephalogram, electromyogram, and electrocardiogram and catheters for measurements of systemic arterial and central venous pressure. Rats were exposed to 90 dB white-noise for 10 min. 90 dB noise exposure resulted in an immediate and significant increase in RSNA while LSNA did not change significantly. There was a significant difference in the response between RSNA and LSNA during the 90 dB noise exposure. Sino-aortic denervation (SAD) attenuated the magnitude of the increase in RSNA while it has no influence on the changes in LSNA observed in SAD rats. These data suggest that the arterial baroreceptor reflex plays a significant role in the differential control of RSNA and LSNA during freezing behaviour in conscious rats.

Differential control of sympathetic nerve activity and hypertension

Once thought to respond uniformly to stimuli (the “fight or flight” effect), the sympathetic nervous system is now considered to be able to exhibit differential control of sympathetic outflow. One emerging hypothesis is that cardiovascular diseases provoke or are exacerbated by selective changes in sympathetic nerve activity (SNA) to specific organs e.g. the kidney. Before this possibility can be considered, we have to assess the ability of different stimuli to provoke selective changes in regional SNA. We explore the possibility that renal SNA and vasomotor SNA in the conscious rabbit are differentially regulated using a range of stimuli including volume expansion, hypoxia and baroreflex activation. We measured SNA to the kidney and the hind limb vasculature (lumbar SNA) in 7 conscious rabbits 6–8 days after the implantation of recording electrodes. Volume expansion (1.5ml/kg/min) resulted in a significant decrease in renal SNA to 66 ± 7% of control levels but no change in lumbar SNA (127 ± 20%). Neither hypoxia (10% O2 and 3% CO2) nor baroreflex curves showed any differential response of renal and lumbar SNA. These results indicate differential control of renal and lumbar SNA in response to acute stimuli and highlight the importance of using a range of stimuli when investigating sympathetic outflow to different regions. Supported by the Health Research Council of New Zealand and Auckland Medical Research Foundation.

Lumbar sympathetic nerve responses to somatopressor reflex activation following hindlimb unloading.

Exposure to space flight or bedrest results in cardiovascular deconditioning which is associated with increased incidence of orthostatic intolerance. Hindlimb unloaded (HU) rats are a model of cardiovascular deconditioning and exhibit reduced sympatho-excitation in response to hypotension. It is possible that other forms of sympathoexcitation are also blunted in HU rats. We hypothesized that sympathoexcitatory responses to somatopressor reflex activation were blunted in HU rats. To test this hypothesis rats were maintained under HU or control conditions (CC) for 14 days (n=4 each). Under Inactin anesthesia the central cut end of the sciatic nerve was stimulated while recording mean arterial pressure (MAP) and lumbar sympathetic nerve activity (LSNA). Sciatic stimulation (10–1000 μA, 15 Hz, 1 ms for 10s) produced intensity dependent increases in MAP and LSNA in both groups. Responses in CC and HU rats were similar. For example, at 250 μA, MAP increased 8±2 mmHg in CC and 8±3 mmHg in HU; LSNA increased 65±17% in CC and 64±29% in HU. At 500, μA MAP increased 15±3 mmHg in CC and 13±3 mmHg in HU; LSNA increased 109±33% in CC and 90±32% in HU. These data suggest that unlike baroreceptor unloading, sympathoexcitatory responses to somatopressor reflex activation are unchanged following cardiovascular deconditioning. Furthermore, blunted baroreflex mediated sympathoexcitation does not appear to be due to a generalized reduction in the ability to increase sympathetic outflow following cardiovascular deconditioning. (Supported by HL 55306, AHA 0650161Z).

Differential sympathetic and angiotensinergic responses in rats submitted to low- or high-salt diet

The present study was designed to evaluate, in Wistar rats, the effect of high- or low-salt diet on the hemodynamic parameters and on the renal and lumbar sympathetic nerve activity. The renal gene expression of the renin angiotensin system components was also evaluated, aiming to find some correlation between salt intake, sodium homeostasis and blood pressure increase. Male Wistar rats received low (0.06% Na, TD 92141-Harlan Teklad), a normal (0.5% Na, TD 92140), or a high-salt diet (3.12% Na, TD 92142) from weaning to adulthood. Hemodynamic parameters such as cardiac output and total peripheral resistance, and the renal and lumbar sympathetic nerve activity were determined ( n = 45). Plasma renin activity, plasma and renal content of angiotensin (ANG) I and II, and the renal mRNA expression of angiotensinogen, renin, AT1 and AT2 receptors were also measured ( n = 24). Compared to normal- and low-salt diet-, high-salt-treated rats were hypertensive and developed an increase ( P < 0.05) in total peripheral resistance and lumbar sympathetic nerve activity. A decrease in renal renin and angiotensinogen-mRNAs and in plasma ANG II and plasma renin activity was also found in salt overloaded animals. The renal sympathetic nerve activity was higher ( P < 0.05) in low- compared to high-salt-treated rats, and was associated with an increase ( P < 0.05) in renal ANG I and II and with a decrease ( P < 0.05) in AT2 renal mRNA. Plasma ANG I and II and plasma renin activity were higher in low- than in normal-salt rats. Our results show that increased blood pressure is associated with increases in lumbar sympathetic nerve activity and total peripheral resistance in high-salt-treated rats. However, in low-salt-treated rats an increase in the renal sympathetic nerve was correlated with an increase in the renal content of ANG I and II and with a decrease in AT2 renal mRNA. These changes are probably in favor of the antinatriuretic response and the sodium homeostasis in the low-salt group.

Exercise training attenuates increases in lumbar sympathetic nerve activity produced by stimulation of the rostral ventrolateral medulla

Exercise training (ExTr) has been associated with blunted activation of the sympathetic nervous system in several animal models and in some human studies. Although these data are consistent with the hypothesis that ExTr reduces the incidence of cardiovascular diseases via reduced sympathoexcitation, the mechanisms are unknown. The rostral ventrolateral medulla (RVLM) is important in control of sympathetic nervous system activity in both physiological and pathophysiological states. The purpose of the present study was to test the hypothesis that ExTr results in reduced sympathoexcitation mediated at the level of the RVLM. Male Sprague-Dawley rats were treadmill trained or remained sedentary for 8-10 wk. RVLM microinjections were performed under Inactin anesthesia while mean arterial pressure, heart rate, and lumbar sympathetic nerve activity (LSNA) were recorded. Bilateral microinjections of the GABA(A) antagonist bicuculline (5 mM, 90 nl) into the RVLM increased LSNA in sedentary animals (169 +/- 33%), which was blunted in ExTr animals (100 +/- 22%, P < 0.05). Activation of the RVLM with unilateral microinjections of glutamate (10 mM, 30 nl) increased LSNA in sedentary animals (76 +/- 13%), which was also attenuated by training (26 +/- 2%, P < 0.05). Bilateral microinjections of the ionotropic glutamate receptor antagonist kynurenate (40 mM, 90 nl) produced small increases in mean arterial pressure and LSNA that were similar between groups. Results suggest that ExTr may reduce increases in LSNA due to reduced activation of the RVLM. Conversely, we speculate that the relatively enhanced activation of LSNA in sedentary animals may be related to the increased incidence of cardiovascular disease associated with a sedentary lifestyle.

A spinal vasopressinergic mechanism mediates hyperosmolality-induced sympathoexcitation.

An elevation in plasma osmolality elicits a complex neurohumoral response, including an activation of the sympathetic nervous system and an increase in arterial pressure. Using a combination of in vivo and in situ rat preparations, we sought to investigate whether hypothalamic vasopressinergic spinally projecting neurones are activated during increases in plasma osmolality to elicit sympathoexcitation. Hypertonic saline (HS, i.v. bolus), which produced a physiological increase in plasma osmolality to 299 +/- 1 mosmol (kg water)(-1), elicited an immediate increase in mean arterial pressure (MAP) (from 101 +/- 1 to 121 +/- 3 mmHg) in vivo. Pre-treatment with prazosin reversed the HS-induced pressor response to a hypotensive response (from 121 +/- 3 to 68 +/- 2 mmHg), indicating significant activation of the sympathetic nervous system. In an in situ arterially perfused decorticate rat preparation, hyperosmotic perfusate consisted of either 135 mm NaCl, or a non-NaCl osmolyte, mannitol (0.5%); both increased lumbar sympathetic nerve activity (LSNA) by 32 +/- 5% (NaCl) and 21 +/- 1% (mannitol), which was attenuated after precollicular transection (7 +/- 3% and 1 +/- 1%, respectively). Remaining experiments used the NaCl hyperosmotic stimulus. In separate preparations the hyperosmotic-induced sympathoexcitation (21 +/- 2%) was also significantly attenuated after transection of the circumventricular organs (2 +/- 1%). Either isoguvacine (a GABA(A) receptor agonist) or kynurenic acid (a non-selective ionotropic glutamate receptor antagonist) microinjected bilaterally into the paraventricular nucleus (PVN) attenuated the increase in LSNA induced by the hyperosmotic stimulus (control: 25 +/- 2%; after isoguvacine: 7 +/- 2%; after kynurenic: 8 +/- 3%). Intrathecal injection of a V(1a) receptor antagonist also reduced the increase in LSNA elicited by the hyperosmotic stimulus (control: 29 +/- 6%; after blocker: 4 +/- 1%). These results suggest that a physiological hyperosmotic stimulus produces sympathetically mediated hypertension in conscious rats. These data are substantiated by the in situ decorticate preparation in which sympathoexcitation was also evoked by comparable hyperosmotic stimulation. Our findings demonstrate the importance of vasopressin acting on spinal V(1a) receptors for mediating sympathoexcitatory response to acute salt loading.

Deoxycorticosterone Acetate–Salt Rats

Using deoxycorticosterone acetate (DOCA)-salt rats, we tested the hypothesis that increased plasma NaCl concentration supports sympathetic activity and blood pressure (BP) during salt-sensitive hypertension. One day before experimentation, femoral catheters and an electrode for measurement of lumbar sympathetic nerve activity (LSNA) probe were surgically positioned in DOCA-salt and Sham-salt rats. DOCA-salt rats exhibited increased (P<0.05) BP and NaCl concentration (BP, 163+/-8 mm Hg; NaCl, 260.8+/-3.3 mEq/L [DOCA-salt]: BP, 106.3+/-4.2 mm Hg; NaCl, 254.3+/-1.7 mEq/L [Sham-salt]). After V1 vasopressin blockade (Manning compound, 5 microg IV), infusion (0.12 mL/min) of 5% dextrose in water decreased NaCl concentrations, BP (-28+/-7 mm Hg), and LSNA (-39+/-5%) in DOCA-salt but not Sham-salt rats. To explain how such small (approximately 2%) increases in plasma NaCl could underlie the hypertension, we hypothesized that DOCA augments the pressor and sympathoexcitatory actions of NaCl. To address this hypothesis, animals with equally elevated NaCl but no DOCA (Sham-1.7% salt) and animals with increased DOCA but normal NaCl levels (DOCA-water) were prepared and administered the infusion of 5% dextrose in water. BP and LSNA were not altered in DOCA-water rats. In the Sham-1.7% salt rats, BP fell (P<0.05), but not LSNA, and the responses were significantly smaller than that observed in the DOCA-salt animals. Collectively, these data suggest that increased NaCl levels contribute to sympathoexcitation and hypertension in DOCA-salt rats because of amplification of the NaCl signal by DOCA.

Chronic intermittent hypoxia (CIH) enhances the lumbar sympathoexcitatory response to central hyperosmotic NaCl

Rats exposed to CIH develop elevated mean arterial pressure (MAP) and sympathetic nerve activity (SNA). Although pro-hypertensive factors such as stress and obesity have been implicated in responses to CIH, little is known regarding interactions of CIH with central effects of Na/osmolality. To investigate this issue, rats were exposed to alternating 3 min periods of normoxia (room air, 21% O2) and hypoxia (10% O2) for 8 hr/day for 7 days. Control rats continuously breathed normoxic air. Rats were then anesthetized and responses of MAP, renal and lumbar SNA to internal carotid artery injection (100 μl) of isotonic (150 mM) and hypertonic (450 mM) NaCl solutions were recorded. In control (n=7) and CIH-exposed (n=7) rats, ICA injection of isotonic NaCl was without effect on all recorded variables. In contrast, ICA injection of hypertonic NaCl significantly increased MAP (P<0.01), renal SNA (P<0.01–0.001) and lumbar SNA (P<0.01–0.001) in control and CIH-exposed rats. When compared across groups, the magnitude of MAP (control: 36±4 mmHg, CIH: 33±4 mmHg) and renal SNA (control: 191±12%, CIH: 194±16%) responses were similar. In contrast, the increase in lumbar SNA was significantly (P<0.05) greater in CIH-exposed (213±32%) rats compared to controls (153±8%). These data suggest that exaggerated sympathetic outflow following CIH may involve central interactions with Na/hyperosmolality. Specifically, CIH may sensitize those neural elements responsive to Na/hyperosmolality that regulate lumbar SNA. Support: HL071645 (GMT), HL66335 (SWM)

Organum vasculosum of the lamina terminalis (OVLT) contributes to sympathoexcitatory responses to central hyperosmolality

To determine effects of OVLT lesions on pressor and sympathetic responses to central hyperosmolality, rats were anesthetized and mean arterial pressure (MAP) and renal sympathetic nerve activity (SNA) were recorded. NaCl solutions (150, 375 and 750 mM) were injected (150 μl) via an internal carotid artery and MAP and renal SNA responses were recorded before, 15 and 60 min after lesioning (500 μA, 45 s) the OVLT (n=6). The location of OVLT was mapped by stimulus (0.5 Hz, 1 ms, 150 μA)-triggered averaging of renal SNA. Before lesion, hypertonic, but not isotonic, NaCl increased MAP (375 mM 11± 2.6 mmHg, 750 mM 21±2.2 mmHg) and renal SNA (375 mM 184±14%, 750 mM: 209±12%) (P<0.001 vs 150 mM). After lesion, renal SNA responses were reduced (P<0.001 vs 150 mM) at 15 min (375mM 135 ± 4%, 750mM 176±7%) and 60 min (375mM 132±8%, 750mM 166±8%). MAP responses were not significantly altered. To exclude a role for ‘fibers en passage’, the OVLT was inactivated with muscimol (100 pmol, 50 nl) (n=4). Before muscimol, hypertonic NaCl increased MAP (375mM 8±3.9 mmHg, 750mM 17±2.8 mmHg) (P<0.05), renal SNA (375mM 147±4%, 750mM 176±10%) and lumbar SNA (375mM 184±23%, 750mM 209±30%) (P<0.001). After muscimol, renal SNA (375mM 119±7%, 750mM 141±12%) and lumbar SNA (375mM 132±9%, 750mM 145±2%) responses were reduced at 15 and 60 min (P<0.001). Again, MAP responses were not altered. Since ICA NaCl elicited consistent responses in sham controls, it appears that lesions/microinjections were effective due to interruption of OVLT activity. We conclude that elevated SNA in response to central hyperosmotic NaCl depends, in part, on OVLT neurons. Support HL071645

Interaction between GABA and excitatory amino acids in control of sympathetic nerve activity by the rostral ventrolateral medulla in hindlimb unloaded rats.

Previously we have reported that pressor and sympathoexcitatory responses to blockade of γ-amino butyric acid (GABAA) receptors in the rostral ventrolateral medulla (RVLM) are enhanced in hindlimb unloaded (HU) rats, a model of cardiovascular deconditioning. Excitatory amino acids (EAAs) may play a role in the sympathoexcitation produced by removal of GABAergic tone in the RVLM. Therefore, we hypothesized that EAAs contribute to enhanced responses to GABAA blockade observed in HU rats. To test this hypothesis, rats were maintained under HU or control conditions for 14 days. Bilateral RVLM microinjections were then performed under Inactin anesthesia while recording mean arterial pressure (MAP) and lumbar sympathetic nerve activity (LSNA). The EAA antagonist kynurenate (40 mM, 90 nl) had little or no effect alone in HU or control rats but attenuated increases in MAP and LSNA produced by bicuculline (5 mM, 90nl) in both groups. However, the response to bicuculline in the presence of kynurenate was enhanced in HU versus control rats. These data suggest that although EAAs play a role in the pressor and sympathoexcitatory responses to GABAA receptor blockade in the RVLM, they do not appear to account for differences observed in control and HU rats. We speculate that differences in GABAA tone and/or non-EAA mediated transmission are responsible for enhanced responses to bicuculline in rats following a period of cardiovascular deconditioning. (Supported by HL-55306, NNA04CC626, NAG21603).

Sympathetic responses to exercise in myocardial infarction: a role played by central command

Central command is a feed-forward neural mechanism originating in higher brain, stimulating medulla, and evoking both motor and cardiorespiratory activation in exercise. Whether this contributes to the exaggerated cardiovascular responses to exercise in heart failure (HF) is unknown. We hypothesized that HF augments sympathetic responses to central command. Thus, renal and lumbar sympathetic nerve activities (RSNA and LSNA) responses to fictive locomotion were examined in healthy control rats (n=8) and rats with myocardial infarction (MI) (≥8 weeks after coronary artery ligation, n=8). Fictive locomotion was evoked by electrical stimulation of mesencephalic locomotor region (MLR) of the decerebrate and paralyzed rats. Mild stimulation (20 μA) of the MLR did not result in significant differences in RSNA and LSNA responses between control and MI groups. Intense stimulation (50 μA) induced greater RSNA and LSNA responses in MI (120 % and 55 %, P<0.05 vs control) as compared with controls (65 % and 15 %). These data suggest that the sympathetic responses to activation of central command are sensitized in HF animals after MI. This study was supported by NIH R01 HL075533 & HL078866 (Li) and HL060800 (Sinoway).

A NOVEL IN SITU APPROACH FOR STUDYING THE HYPOTHALAMIC CONTROL OF HYPEROSMOLALITY INDUCED SYMPATHOEXCITATION

Several studies have shown that changes in plasma osmolality have an influence on the sympathetic nervous system, and that hypothalamic areas such as the paraventricular nucleus (PVN) play a significant role in these homeostatic adjustments. The aim of this study was to assess the role of the PVN in regulating sympathetic outflow in response to physiological hyperosmotic stimuli in a novel in situ decorticated arterially perfused preparation of rat. Rats (70–90g) were anaesthetised with halothane and decorticated, which included removal of the thalamus. The systemic osmotic stimulus was delivered by changing the perfusate (Ringer’s solution) from isotonic (290 mOsmol) to hypertonic (320 mOsmol) over 40s. This stimulus caused an increase in lumbar sympathetic nerve activity (LSNA; 29.3±5 %, n=10), which persisted until the isotonic perfusate was re-introduced. Following ablation of the hypothalamic paraventricular nucleus (PVN) hyperosmotic-induced sympatho-excitation was blunted in magnitude (11±3%, n=6). Bilateral PVN microinjections of either isoguvacine (60 nmol/60nl), for reversible inactivation, or blockade of ionotropic glutamate receptors (kynurenic acid; 6 μmol/60nl) both attenuated the hypertonic-induced increase in LSNA to 7±2% and 8±3%, respectively, from control (25±2%, n=5). In conclusion, we have demonstrated that the in situ preparation demonstrates appropriate responses to physiologically relevant osmolality changes as seen in vivo during acute salt-loading. Moreover, the PVN plays a major role in hyperosmotic-induced sympatho-excitation. British Heart Foundation funded research

Role of arterial baroreceptor in regulating renal and lumbar sympathetic nerve activity during normal daily activity in rats

Role of arterial baroreceptor in regulating renal and lumbar sympathetic nerve activity during normal daily activity in rats

Differential control of renal and lumbar sympathetic nerve activity during freezing behaviour in rats

Differential control of renal and lumbar sympathetic nerve activity during freezing behaviour in rats

Captopril does not affect reflex increases in adrenal or lumbar sympathetic nerve activity to hypoglycemia in rats

Blockade of angiotensin II (ANGII) receptors or converting enzyme inhibition attenuates reflex increases in epinephrine during insulin-induced hypoglycemia. Because ANGII receptors are found in several sites within the central nervous system, the aim of this study was to examine whether acute captopril attenuates the reflex increase in adrenal preganglionic sympathetic nerve activity (SNA) induced by hypoglycemia. We infused vehicle (control) or insulin (30 U/kg IV) in anesthetized rats or in rats pretreated with captopril (Cap-insulin; 2.5 mg/kg, then 1 mg/kg per hour IV) while measuring hemodynamics and SNA from adrenal preganglionic, adrenal postganglionic, and lumbar sympathetic nerves. Hypoglycemia elicited similar adrenal preganglionic SNA increases in insulin-treated (260% ± 31% from 100% baseline) and Cap-insulin–treated (255% ± 34%) rats. Likewise, increases in adrenal postganglionic SNA and lumbar SNA were equivalent in the insulin and Cap-insulin groups. Hypoglycemia also elicited a tachycardia in insulin-treated rats that was attenuated in Cap-insulin–treated rats, and corresponding blood pressure decreases in insulin rats were enhanced in Cap-insulin–treated rats. Thus, blockade of ANGII formation by captopril did not affect hypoglycemia-induced activation of adrenal preganglionic SNA, indicating that the renin-angiotensin systems in the brain and spinal cord do not modulate increases in adrenal SNA during hypoglycemia.

Evidence of differential control of renal and lumbar sympathetic nerve activity in conscious rabbits

We have explored the possibility that renal sympathetic nerve activity (RSNA) and vasomotor sympathetic nerve activity are differentially regulated. We measured sympathetic nerve activity (SNA) to the kidney and the hind limb vasculature in seven conscious rabbits 6-8 days after the implantation of recording electrodes. Acute infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) (6 mg.kg(-1).min(-1) for 5 min) led to an increase in blood pressure (from 66 +/- 1 to 82 +/- 3 mmHg) and a decrease in heart rate (from 214 +/- 15 to 160 +/- 13 bpm). L-NAME administration caused a significantly greater decrease in RSNA than lumbar sympathetic nerve activity (LSNA) (to 68 +/- 14% vs. 84 +/- 4% of control values, respectively). Volume expansion (1.5 ml.kg(-1).min(-1)) resulted in a significant decrease in RSNA to 66 +/- 7% of control levels but no change in LSNA (127 +/- 20%). There was no difference in the gain of the baroreflex curves between the LSNA and RSNA [maximum gain of -7.6 +/- 0.4 normalized units (nu)/mmHg for LSNA vs. -7.9 +/- 0.75 nu/mmHg for RSNA]. A hypoxic stimulus (10% O2 and 3% CO2) led to identical increases in both RSNA and LSNA (195 +/- 40% and 158 +/- 21% of control values, respectively). Our results indicate tailored differential control of RSNA and LSNA in response to acute stimuli.

Putative role of the NTS in alterations in neural control of the circulation following exercise training in rats

Exercise training (ExTr) has been associated with alterations in neural control of the circulation, including effects on arterial baroreflex function. The nucleus tractus solitarius (NTS) is the primary termination site of cardiovascular afferents and critical in the regulation of baroreflex-mediated changes in heart rate (HR) and sympathetic nervous system outflow. The purpose of the present study was to determine whether ExTr is associated with alterations in neurotransmitter regulation of neurons involved in control of cardiovascular function at the level of the NTS. We hypothesized that ExTr would increase glutamatergic and reduce GABAergic transmission in the NTS and that, collectively, these changes would result in a greater overall sympathoinhibitory drive from the NTS in ExTr animals. To test these hypotheses, male Sprague-Dawley rats were treadmill trained or maintained under sedentary conditions for 8-10 wk. NTS microinjections were performed in Inactin-anesthetized animals instrumented to record mean arterial pressure (MAP), HR, and lumbar sympathetic nerve activity (LSNA). Generalized activation of the NTS with unilateral microinjections of glutamate (1-10 mM, 30 nl) produced dose-dependent decreases in MAP, HR, and LSNA that were unaffected by ExTr. Bilateral inhibition of NTS with the GABAA agonist muscimol (1 mM, 90 nl) produced increases in MAP and LSNA that were blunted by ExTr. In contrast, pressor and sympathoexcitatory responses to bilateral microinjections of the ionotropic glutamate receptor antagonist, kynurenate (40 mM, 90 nl), were similar between groups. Bradycardic responses to bilateral microinjections of the GABAA antagonist bicuculline (0.1 mM, 90 nl) were attenuated by ExTr. These data indicate that alterations in neurotransmission at the level of the NTS contribute importantly to regulation of HR and LSNA in ExTr animals. In addition to alterations at NTS, these experiments suggest indirectly that changes in other cardiovascular nuclei contribute to the observed alterations in neural control of the circulation following ExTr.