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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Sympathetic nerve activity in the superior cervical ganglia increases in response to imposed increases in arterial pressure

Ritchie Centre for Baby Health Research, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia

Submitted 10 May 2007 ; accepted in final form 22 January 2008

	ABSTRACT

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Sympathetic vasoconstriction of cerebral vessels has been proposed to be a protective mechanism for the brain, limiting cerebral perfusion and microcirculatory pressure during transient increases in arterial pressure. To furnish direct neural evidence for this proposition, we aimed to develop a method for recording cerebral sympathetic nerve activity (SNA) from the superior cervical ganglion (SCG). We hypothesized that SNA recorded from the SCG increases during imposed hypertension, but not during hypotension. Lambs (n = 11) were anesthetized (-chloralose, 20 mg·kg^–1·h^–1) and ventilated. SNA was measured using 25-µm tungsten microelectrodes inserted into the SCG. Arterial blood pressure (AP) was pharmacologically raised (adrenaline, phenylephrine, or ANG II, 1–50 µg/kg iv), mechanically raised (intravascular balloon in the thoracic aorta), or lowered (sodium nitroprusside, 1–50 µg/kg iv). In response to adrenaline (n = 10), mean AP increased 135 ± 10% from baseline (mean ± SE), and the RMS value of SNA (Square Root of the Mean of the Squares, SNA_RMS) increased 255 ± 120%. In response to mechanically induced hypertension, mean AP increased 43 ± 3%, and SNA_RMS increased 53 ± 13%. Generally, (9 of 10 animals), SNA_RMS did not increase, as AP was lowered with sodium nitroprusside. Using a new model for direct recording of cerebral SNA from the SCG, we have demonstrated that SNA increases in response to large induced rises, but not falls, in AP. These findings furnish direct support for the proposed protective role for sympathetic nerves in the cerebral circulation.

cerebral circulation; hypertension; sympathetic nervous system; adrenaline; lamb

Despite these intensive investigations, the exact functional role of the sympathetic nervous system in the regulation of the cerebral circulation remains an issue of debate (32). Sympathetic vasoconstriction of cerebral vessels has been proposed to be a protective mechanism for the brain, limiting cerebral perfusion and microcirculatory pressure during transient increases in arterial pressure (4, 14, 22). Stimulation of the sympathetic trunk immediately caudal to the SCG during periods of acute hypertension limits the resulting increase in cerebral blood flow in several studies (6, 22, 36).

Large natural increases in arterial pressure can occur during sympathetically dominated conditions such as during weightlifting, sexual activity (30), and, as recently recognized, during REM sleep (35), and REM sleep disrupted by apnea (34). Cerebral sympathetic activity appears to limit cerebral perfusion during normal sleep, as baseline cerebral blood flow, as well as the blood flow surges occurring during the natural transient blood pressure surges of REM sleep are augmented after cervical (SCG) sympathectomy in sleeping lambs (27).

As yet, there is no animal model available to directly assess possible protective roles for sympathetic activity during natural increases of cerebral perfusion pressure. To date, direct neural recordings have been limited to single-unit recordings from SCG neurons in anesthetized preparations (26, 29). Although this method has provided important insights into SCG neuron discharge patterns, they are not practicable in anesthetized, freely moving animals.

Accordingly, our aim was to develop a method for recording cerebral sympathetic nerve activity (SNA) in the anesthetized lamb that could be adapted for subsequent use in the conscious lamb. Additionally, we aimed to use this model to further examine the protective role of cerebral SNA first proposed by Busija et al. (6). We hypothesized that cerebral SNA recorded from the SCG increases during periods of induced hypertension, but not hypotension, and we tested the hypothesis during pharmacological and mechanical manipulations of systemic arterial pressure.

	MATERIALS AND METHODS

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General Procedures

Studies were conducted on eleven Merino/Border-Leicester lambs (1–2 wk old, 4–8 kg body wt). Anesthesia was induced with ketamine (5 mg/kg iv) and -chloralose (40 mg/kg iv loading dose) and maintained for the duration of the experiment by infusion of -chloralose (20 mg·kg^–1·h^–1 iv) (Sigma, St. Louis, MO). All surgical and experimental procedures were performed in accordance with the guidelines of the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes established by the National Health and Medical Research Council of Australia and were approved by the Monash University-Monash Medical Centre Committee on Ethics in Animal Experimentation.

Lambs were placed supine and artificially ventilated with oxygen-enriched room air through an endotracheal tube. Arterial oxygen saturation (Nellcor Pulse Oximeter, Hayward, CA), end tidal CO₂, endotracheal pressure, and rectal temperature (U-lab Instruments, Port Louis, Mauritius) were monitored to ensure adequate anesthesia. Arterial blood pressure was monitored continuously through a radial artery catheter connected to a calibrated strain gauge manometer (Cobe CDX III, Cobe Laboratories, Lakewood, CO) referenced to the lamb's midthoracic level. Pressure signals were low-pass filtered at 100 Hz.

An intra-arterial balloon (Fogarty Dilation Atrioseptostomy Catheter, 5F; Baxter Healthcare, Santa Ana, CA) was surgically inserted via the femoral artery into the caudal abdominal aorta.

Sympathetic Nerve Recording

The SCG was accessed via a midline neck incision made caudal to the level of the jaw. The vagus nerve was located and followed to the point at which the cervical sympathetic trunk visibly separated to continue on to the SCG. The SCG was located, and a pair of lightweight, Teflon-coated tungsten microelectrodes (25-µm shaft diameter, 1 mm bared tip) (California Fine Wire, Grover Beach, CA) was inserted into its cranial aspect. A separate stainless steel electrode was attached onto nearby tissue as a ground reference electrode.

The neural signal was amplified (25,000 times) and to minimize low-frequency noise filtered (100–2000 Hz) using Cyberamp (Axon Instruments, Foster City, CA) and together with pressure signals was digitized and recorded at a sampling frequency of 10 kHz, using a data acquisition-recording system (Powerlab, ver. 5.3, ADI Instruments, Carrollton, TX). Chart ver. 5.3 was used for storage and off-line analysis, including power spectral analysis, which was performed on the RMS (Root Mean Square) of the neural signal.

Experimental Protocol

Acute hypertension was induced pharmacologically (adrenaline, phenylephrine, or ANG II, Sigma) with a range of doses (1–50 µg/kg iv) or mechanically with inflation of the intra-arterial balloon. Hypotension was induced pharmacologically with a vasodilator (sodium nitroprusside, 1–50 µg/kg iv, Sigma). At least 5 min were allowed between pressor and depressor tests for blood pressure to return to baseline levels.

While recording SNA, animals were killed at the end of each experiment with an overdose of pentobarbital sodium (150 mg/kg iv).

Data Analysis

Arterial blood pressure (AP) was averaged in second-by-second segments. The RMS of the raw SNA signal (Square Root of the Mean of the Squares, SNA_RMS) was calculated second by second using Chart ver. 5.3 (ADI Instruments).

Responses to vasoconstrictor drug injections and balloon inflations are expressed as peak % change from a baseline value averaged over 30 s before each test. The onset of the mean AP (MAP) increase was defined as the first of three consecutive increases immediately following drug injection or balloon inflation. The onset of SNA_RMS change was defined as the first of three consecutive time points, which exceeded 5% of the baseline value following onset of the MAP increase. To examine the relationship between SNA_RMS and MAP, data from repeated tests in each lamb were expressed as % changes, averaged for each lamb, and then assigned into bins of 25% across the MAP range. SNA_RMS changes after sodium nitroprusside, intra-arterial balloon deflation, or post mortem were obtained by averaging over 10 s when AP reached its minimum value. A trendline was fitted through pharmacological data and intra-arterial balloon data using a fourth-order polynomial (Excel, Microsoft Corp, Redmond WA).

Statistics

Values are reported as means ± SE. Changes of SNA from baseline were compared using a paired Student's t-test or a Wilcoxon signed-ranks test if data were not normally distributed (SigmaStat for Windows, Systat Software Inc., Richmond VA). P < 0.05 was considered significant.

	RESULTS

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Animal Characteristics

Recordings from the SCG were obtained in five male and six female lambs. At the beginning of the experiment MAP was 77.5 ± 4.4 mmHg, body weight was 6.1 ± 0.4 kg, and mean age was 10.1 ± 1.4 days. Body temperature and arterial blood gases were close to normal physiological levels (temperature, 39.0 ± 0.4°C; arterial PO₂, 157.0 ± 7.2 mmHg; PCO₂, 34.4 ± 2.2 mmHg; and pH, 7.4 ± 0.0).

Responses to Hypertension and Hypotension

Adrenaline. An example of the pattern of the change in SNA during adrenaline-induced hypertension is illustrated in Fig. 1. Increased AP was associated with an increase in SNA amplitude (µV) beginning when AP had increased by 50 mmHg above a baseline level of 70 mmHg (top). After reaching its peak, cyclic AP modulation associated with the ventilator cycle was reflected in a clear modulation of the SNA trace. SNA spectral power (µV²) in the range of 0–10 Hz (bottom) was 200 times greater at peak AP than at baseline AP. The ventilator-related modulation evident in the raw neural signal was reflected in a spectral peak at the ventilator frequency (0.4 Hz). There was a very small contribution to total SNA power at heart frequency (3–4 Hz).

View larger version (25K): [in this window] [in a new window]   Fig. 1. Illustrative arterial blood pressure (AP) recording and sympathetic nerve activity (SNA) neurogram during three periods with varied AP. Top: SNA response to pharmacologically induced hypertension (adrenaline, 15 µg/kg iv, arrow). Onset of the AP increase (depicted by the dashed line) is followed by an SNA increase when AP reaches 120 mmHg. Note the prominent ventilatory modulation of AP, which is reflected in a modulation of SNA at AP levels above 120 mmHg. Middle: lower SNA at baseline levels of AP and the prompt decline of SNA to near zero on killing the animal (pentobarbital sodium, 150 mg/kg iv), while artificial ventilation is continued (Airway Pressure, Paw). Note the smaller ordinate scale for SNA. Bottom: power spectra at 0–10 Hz for the three differing levels of AP (A–C) seen in the upper and middle panels. SNA power (µV2) is much greater (by a factor of 200) at high blood pressure (A) than at the lower baseline blood pressure (B). Ventilatory modulation of the SNA signal is reflected in a prominent peak at the ventilator frequency of 0.4 Hz (A). Note the smaller ordinate scale for spectra B and C. Also note that the SNA signal declines promptly to near zero after death of the animal (C). Postmortem (C), power is 1/3,000 of the level evident at high blood pressure (A) and 1/15 the level at baseline pressure (B). The low level of SNA recorded during period C, when lung ventilation continued after the animal was killed, signifies that ventilator-induced movement and recording system noise make negligible additions to the biological SNA signal.

View larger version (17K): [in this window] [in a new window]   Fig. 2. Coherent averages ± SE of mean arterial pressure (MAP) and SNARMS (root mean square) in response to adrenaline (n = 10, arrow). The dashed line represents the onset of MAP increase after adrenaline injection. The onset of SNARMS increase occurred when MAP increased by 56% above baseline.

View larger version (17K): [in this window] [in a new window]   Fig. 3. AP recordings and SNA neurograms obtained during pharmacological manipulation of AP. Hypertension induced with phenylephrine (A) (10 µg/kg iv, arrow); ANG II (B) (5 µg/kg iv, arrow) Hypotension induced with sodium nitroprusside (C) (25 µg/kg iv, arrow).

View larger version (26K): [in this window] [in a new window]   Fig. 4. Illustrating an exceptional study in a single lamb of the nine studied in which SNA increased (rather than remaining unchanged) during nitroprusside-induced hypotension (A) (25 µg/kg iv, arrow) and decreased (rather than increased) during adrenaline-induced hypertension (B) (50 µg/kg iv, arrow).

View larger version (16K): [in this window] [in a new window]   Fig. 5. Illustration of AP recording and SNA neurogram during hypertension induced mechanically with inflation of an intra-arterial balloon. The dashed box represents the period of balloon inflation. Note the close correspondence of SNARMS with MAP.

View larger version (10K): [in this window] [in a new window]   Fig. 6. Coherent averages ± SE of MAP and SNARMS during intra-arterial balloon inflation (dashed box, n = 3). Note the close correspondence of SNARMS with MAP. The onset of SNARMS increase occurs when MAP increases to 38% above baseline.

View larger version (11K): [in this window] [in a new window]   Fig. 7. The relationship between SNARMS over a wide range of MAP. MAP was increased and decreased pharmacologically with adrenaline (, n = 10), ANG II (, n = 3) or sodium nitroprusside (, n = 8), respectively or mechanically with intra-arterial balloon inflation (, n = 3). Post mortem value (, n = 8) shows a 15% decrease in SNARMS. Note that SNARMS increases when MAP is raised by 40–60% but not when MAP is reduced.

	DISCUSSION

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An increase in SNA was consistently recorded from the SCG in response to a range of vasoconstrictor pharmacological agents, comprising adrenaline, phenylephrine, and ANG II. SNA also increased when arterial pressure was raised mechanically by inflation of an intra-arterial balloon. A variety of methods of raising arterial pressure were examined to exclude the possibility that pharmacological stimulation of known receptors within the SCG was involved in mediating the SNA response. ANG II receptors, as well as -adrenoceptors, are found on sympathetic neurons and have been shown to mediate synaptic transmission (8, 37, 38); hence, SNA increases recorded during hypertension were potentially due to ANG II receptor or vascular ₂-adrenoceptor stimulation. However, as SNA also increased with hypertension induced by intra-arterial balloon inflation, receptor stimulation cannot account for the increases in SNA observed (Fig. 7).

With the exception of one lamb, all methods of raising AP induced SNA increases in a similar pattern, with the augmentation of SNA beginning at an apparent AP threshold, rather than after a fixed delay following the onset of the AP increase. Threshold values of AP averaged 40 mmHg (56%) above baseline with adrenaline injections (Fig. 2); the corresponding values were 36 mmHg and 40% in balloon inflations (Fig. 6). The time of SNA increase was evidently related to the slope of the AP increase: being delayed when AP rose slowly, as exemplified in Fig. 1 or prompt when AP rose rapidly as with balloon inflation (Fig. 5). Further evidence for the presence of a threshold was provided by the respiratory modulation of SNA that was present at elevated AP but not at baseline pressure (Fig. 1).

Arterial baroreceptors are the likely candidates for receptors that would signal a sudden increase in AP above a set threshold and trigger a reflex increase in cerebral SNA. Previously, a baroreceptor mechanism has been demonstrated to mediate SNA modulation arising from cyclic blood pressure variations associated with artificial ventilation (17). The basis of the ventilatory modulation of SNA observed in our study is also likely to be explained by baroreceptor stimulation, as the modulating effect was most prominent at high levels of AP and as baroreceptors are involved in the translation of ventilatory activity to modulation of AP (17, 26). Ventilatory modulation of SNA was infrequent in our study, at variance with a previous study in which it was present in most fibers of the sympathetic trunk of rats (17) but in keeping with another in which it was rare in neurons supplying the hind limb (18). Possibly, ventilatory modulation of SNA in our study may have been increased if the cyclic variation of AP was enhanced, as has been found in the rat (19).

Threshold values for the onset of SNA_RMS were reached when AP was increased by 40–60% above baseline (Fig. 7), equivalent to a mean arterial pressure of 100–115 mmHg. This threshold value is similar to the upper limit of cerebral blood flow autoregulation in the lamb of 100 mmHg (23, 31). Speculatively, exceeding the upper AP limit of the autoregulation curve may also be the trigger for a reflex increase in cerebral sympathetic vasoconstrictor activity. The functional significance of a threshold for augmented SNA may be protection of the cerebral microvasculature against high perfusion pressure.

Importantly, we found essentially no evidence for activation of cerebral SNA in response to systemic hypotension. In the majority of studies, SNA activity increased as pressure rose but did not increase as arterial pressure was lowered, suggesting that the population of SCG neurons that we sampled was activated in a pressure-protective pattern specific to the brain and not as a component of a widespread, systemic reflex restoration of arterial pressure. Exceptionally, in a single lamb, we observed a reversed pattern of SNA responses to AP variation. In this lamb, hypertension resulted in a decrease of SNA, while hypotension did elicit an increase in SNA, a pattern that would be typical of neurons involved in systemic pressure regulation.

With the intention of mainly sampling neurons innervating cerebral vessels, we inserted electrodes into the cranial aspect of the SCG, as this region predominantly contains neurons projecting to the brain. Of the total population of neurons in this region of the ganglion, as many as 75% project to the internal carotid nerve (ICN) (5, 15, 21, 28). Of the ICN-derived fibers, the overwhelming majority (90%) are likely to innervate cerebral vessels, based on the much greater mass and blood flow of the brain compared with the other tissues innervated by the ICN, principally skin (33). Though we did not ascertain the structures innervated by the recording neurons, in the exceptional lamb in which an increase in SNA was observed with hypotension, it is likely that the microelectrodes were sampling the remaining 25% of neurons innervating extra-cerebral structures, such as the eye, which respond to hypotension with vasoconstriction (9).

In developing the SNA recording method, we excluded movement artifact as the primary source of the SNA signal by filtering low frequencies, carefully securing electrodes, and by performing measurements during brief interruptions and modifications of lung ventilation, the principal source of movement. Significant SNA power was observed at 0–10 Hz, consistent with previous descriptions of the action potential firing rates of sympathetic neurons, which are typically <10 Hz (25, 29). In a control study, SNA power was 200-fold greater at elevated levels of blood pressure than at baseline pressure and promptly fell to zero when the animal was killed, while the lung continued to be ventilated (Fig. 1). The disappearance of the electrical signal post mortem excludes ventilator-induced movement (and amplifier noise) as the primary source of the SNA signal. Additionally, the time delay between the onset of AP elevation and the rise in SNA, together with the small amount of spectral power in the range of heart frequencies, excludes pulsatile movement artifact from nearby arteries as a contaminant of SNA.

Tonic SNA was present in these preparations, as demonstrated by a slight (15%) decrease in the SNA signal post mortem. Previous studies have shown the presence of tonic SNA from single-unit recordings in the SCG (24, 29). As some anesthetic agents have been shown to suppress autonomic nervous activity (20), tonic SNA may be more pronounced in conscious animals. Supporting this suggestion, SCG ablation increased baseline cerebral blood flow by 1/3 in lambs undergoing spontaneous sleep-wake cycles in the study of Loos et al. (27).

These new data provide additional support for the concept that the sympathetic nervous system plays a protective role in the cerebral circulation by preventing excessive perfusion. Stimulation of the sympathetic trunk during acute hypertension limits increases in cerebral blood flow (4, 6, 41). Cervical ganglionectomy has been shown to result in elevated baseline CBF, as well as greater CBF increases associated with natural blood pressure surges (27). Until the present study, no evidence based on direct neural recordings of SNA during potentially damaging elevations in AP was available. Together, these studies suggest that natural sympathetic activation may protect the brain from excessive blood flow, raised microcirculatory pressure, edema, and hemorrhage.

Perspectives and Significance

SNA directed to cerebral vessels increases with acute hypertension, but not with hypotension, suggesting that it serves a protective function for the cerebral microcirculation, and not a regulatory role for maintenance of systemic arterial pressure. Measurement of cerebral SNA in a conscious, spontaneously behaving animal would enable the "protective hypothesis" to be examined during natural increases of cerebral perfusion pressure, such as those that occur commonly in REM sleep and sleep disrupted by conditions such as obstructive sleep apnea (16, 34).

	GRANTS

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This work was supported by the National Health and Medical Research Council of Australia.

	ACKNOWLEDGMENTS

 
We express our gratitude to Vojta Brodecky and Dr. Susan Feng for expert technical assistance.

	FOOTNOTES

 

Address for reprint requests and other correspondence: A. M. Walker, Ritchie Centre for Baby Health Research, Monash Institute of Medical Research, Level 5, Monash Medical Centre, 246 Clayton Rd., Clayton, Melbourne, VIC 3168, Australia (e-mail: adrian.walker{at}med.monash.edu.au)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

	REFERENCES

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1. Arbab MA, Wiklund L, Svendgaard NA. Origin and distribution of cerebral vascular innervation from superior cervical, trigeminal and spinal ganglia investigated with retrograde and anterograde WGA-HRP tracing in the rat. Neuroscience 19: 695–708, 1986.[CrossRef][Web of Science][Medline]
2. Auer LM, Edvinsson L, Johansson BB. Effect of sympathetic nerve stimulation and adrenoceptor blockade on pial arterial and venous calibre and on intracranial pressure in the cat. Acta Physiol Scand 119: 213–217, 1983.[Web of Science][Medline]
3. Bevan R, Dodge J, Nichols P, Poseno T, Vijayakumaran E, Wellman T, Bevan JA. Responsiveness of human infant cerebral arteries to sympathetic nerve stimulation and vasoactive agents. Pediatr Res 44: 730–739, 1998.[Web of Science][Medline]
4. Bill A, Linder J. Sympathetic control of cerebral blood flow in acute arterial hypertension. Acta Physiol Scand 96: 114–121, 1976.[Web of Science][Medline]
5. Bowers CW, Zigmond RE. Localization of neurons in the rat superior cervical ganglion that project into different postganglionic trunks. J Comp Neurol 185: 381–391, 1979.[CrossRef][Web of Science][Medline]
6. Busija DW, Heistad DD, Marcus ML. Effects of sympathetic nerves on cerebral vessels during acute, moderate increases in arterial pressure in dogs and cats. Circ Res 46: 696–702, 1980.[Free Full Text]
7. Busija DW, Leffler CW, Wagerle LC. Responses of newborn pig pial arteries to sympathetic nervous stimulation and exogenous norepinephrine. Pediatr Res 19: 1210–1214, 1985.[CrossRef][Web of Science][Medline]
8. Castren E, Kurihara M, Gutkind JS, Saavedra JM. Specific angiotensin II binding sites in the rat stellate and superior cervical ganglia. Brain Res 422: 347–351, 1987.[CrossRef][Web of Science][Medline]
9. Chou P, Lu DW, Chen JT. Bilateral superior cervical ganglionectomy increases choroidal blood flow in the rabbit. Ophthalmologica 214: 421–425, 2000.[CrossRef][Web of Science][Medline]
10. Edvinsson L, Hamel E. Perivascular nerves in brain vessels. In: Cerebral Blood Flow and Metabolism, edited by Edvinsson L, and Krause D. Philadelphia: Lippincott, Williams & Wilkins, 2002.
11. Edvinsson L, MacKenzie ET, McCulloch J. Adrenergic mechanisms In: Cerebral Blood Flow and Metabolism, edited by Edvinsson L, MacKenzie ET, and McCulloch J. New York: Raven Press, 1993.
12. Edvinsson L, McCulloch J, Uddman R. Feline cerebral veins and arteries: comparison of autonomic innervation and vasomotor responses. J Physiol 325: 161–173, 1982.[Abstract/Free Full Text]
13. Edvinsson L, Nielsen KC, Owman C, West KA. Evidence of vasoconstrictor sympathetic nerves in brain vessels of mice. Neurology 23: 73–77, 1973.[Free Full Text]
14. Edvinsson L, Owman C, Siesjo B. Physiological role of cerebrovascular sympathetic nerves in the autoregulation of cerebral blood flow. Brain Res 117: 519–523, 1976.[CrossRef][Web of Science][Medline]
15. Flett DL, Bell C. Topography of functional subpopulations of neurons in the superior cervical ganglion of the rat. J Anat 177: 55–66, 1991.[Web of Science][Medline]
16. Grant D, Franzini C, Wild J, Walker A. Continuous measurement of blood flow in the superior sagittal sinus of the lamb. Am J Physiol Regul Integr Comp Physiol 269: R274–R279, 1995.[Abstract/Free Full Text]
17. Habler HJ, Bartsch T, Janig W. Two distinct mechanisms generate the respiratory modulation in fibre activity of the rat cervical sympathetic trunk. J Auton Nerv Syst 61: 116–122, 1996.[CrossRef][Web of Science][Medline]
18. Habler HJ, Janig W, Krummel M, Peters OA. Respiratory modulation of the activity in postganglionic neurons supplying skeletal muscle and skin of the rat hindlimb. J Neurophysiol 70: 920–930, 1993.[Abstract/Free Full Text]
19. Habler HJ, Janig W, Michaels M. Respiratory modulation in the activity of sympathetic neurons. Prog Neurobiol 43: 567–606, 1994.[CrossRef][Web of Science][Medline]
20. Halinen MO, Hakumaki MO, Sarajas HS. Suppresion of autonomic postganglionic discharges by pentobarbital in dogs, with or without endotoxemia. Acta Physiol Scand 104: 167–174, 1978.[Web of Science][Medline]
21. Headley DB, Suhan NM, Horn JP. Rostro-caudal variations in neuronal size reflect the topography of cellular phenotypes in the rat superior cervical sympathetic ganglion. Brain Res 1057: 98–104, 2005.[CrossRef][Web of Science][Medline]
22. Heistad DD, Marcus ML, Gross PM. Effects of sympathetic nerves on cerebral vessels in dog, cat, and monkey. Am J Physiol Heart Circ Physiol 235: H544–H552, 1978.[Abstract/Free Full Text]
23. Helou S, Koehler RC, Gleason CA, Jones MD Jr, Traystman RJ. Cerebrovascular autoregulation during fetal development in sheep. Am J Physiol Heart Circ Physiol 266: H1069–H1074, 1994.[Abstract/Free Full Text]
24. Ivanov A, Purves D. Ongoing electrical activity of superior cervical ganglion cells in mammals of different size. J Comp Neurol 284: 398–404, 1989.[CrossRef][Web of Science][Medline]
25. Janig W. Ganglionic transmission in vivo. In: Autonomic Ganglia, edited by McLachlan EM. Luxemburg: Harwood Academic, 1995.
26. Janig W. Pre- and postganglionic vasoconstrictor neurons: differentiation, types, and discharge properties. Annu Rev Physiol 50: 525–539, 1988.[CrossRef][Web of Science][Medline]
27. Loos N, Grant D, Wild J, Paul S, Barfield C, Zoccoli G, Franzini C, Walker A. Sympathetic nervous control of the cerebral circulation in sleep. J Sleep Res 14: 275–283, 2005.[CrossRef][Web of Science][Medline]
28. Luebke JI, Wright LL. Characterization of superior cervical ganglion neurons that project to the submandibular glands, the eyes, and the pineal gland in rats. Brain Res 589: 1–14, 1992.[CrossRef][Web of Science][Medline]
29. McLachlan E, Davies P, Habler H, Jamieson J. On-going and reflex synaptic events in rat superior cervical ganglion cells. J Physiol 501: 165–182, 1997.[Abstract/Free Full Text]
30. Muller JE, Kaufmann PG, Luepker RV, Weisfeldt ML, Deedwania PC, Willerson JT. Mechanisms precipitating acute cardiac events: review and recommendations of an NHLBI workshop. National Heart, Lung, and Blood Institute Mechanisms Precipitating Acute Cardiac Events Participants. Circulation 96: 3233–3239, 1997.[Free Full Text]
31. Papile LA, Rudolph AM, Heymann MA. Autoregulation of cerebral blood flow in the preterm fetal lamb. Pediatr Res 19: 159–161, 1985.[Web of Science][Medline]
32. Sandor P. Nervous control of the cerebrovascular system: doubts and facts. Neurochem Int 35: 237–259, 1999.[CrossRef][Web of Science][Medline]
33. Smolich JJ, Soust M, Berger PJ, Walker AM. Indirect relation between rises in oxygen consumption and left ventricular output at birth in lambs. Circ Res 71: 443–450, 1992.[Abstract/Free Full Text]
34. Somers V, Dyken M, Clary M, Abboud F. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 96: 1897–1904, 1995.[Web of Science][Medline]
35. Somers VK, Dyken ME, Mark AL, Abboud FM. Sympathetic-nerve activity during sleep in normal subjects. N Engl J Med 328: 303–307, 1993.[Abstract/Free Full Text]
36. Tuor U. Local distribution of the effects of sympathetic stimulation on cerebral blood flow in the rat. Brain Res 529: 224–231, 1990.[CrossRef][Web of Science][Medline]
37. Vidovic M, Cohen D, Hill CE. Identification of alpha 2 adrenergic receptor gene expression in sympathetic neurones using polymerase chain reaction and in situ hybridization. Brain Res Molec Brain Res 22: 49–56, 1994.[Medline]
38. Vidovic M, Hill CE. Transient expression of alpha-1B adrenoceptor messenger ribonucleic acids in the rat superior cervical ganglion during postnatal development. Neuroscience 77: 841–848, 1997.[CrossRef][Web of Science][Medline]
39. Wagerle L, Kurth C, Roth R. Sympathetic reactivity of cerebral arteries in developing fetal lamb and adult sheep. Am J Physiol Heart Circ Physiol 258: H1432–H1438, 1990.[Abstract/Free Full Text]
40. Wagerle LC, Heffernan TM, Sacks LM, Delivoria-Papadopoulos M. Sympathetic effect on cerebral blood flow regulation in hypoxic newborn lambs. Am J Physiol Heart Circ Physiol 245: H487–H494, 1983.[Free Full Text]
41. Waldemar G, Paulson OB, Barry DI, Knudsen GM. Angiotensin converting enzyme inhibition and the upper limit of cerebral blood flow autoregulation: effect of sympathetic stimulation. Circ Res 64: 1197–1204, 1989.[Abstract/Free Full Text]

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