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J Appl Physiol 95: 1986-1993, 2003. First published July 25, 2003; doi:10.1152/japplphysiol.00438.2003
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Forebrain and brain stem neural circuits contribute to altered sympathetic responses to heating in senescent rats

Michael J. Kenney and Richard J. Fels

Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506

Submitted 1 May 2003 ; accepted in final form 18 July 2003


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 DISCLOSURES
 ACKNOWLEDGMENTS
 REFERENCES
 
Acute heating in young rats increases visceral sympathetic nerve discharge (SND); however, renal and splanchnic SND responses to hyperthermia are attenuated in senescent compared with young Fischer 344 (F344) rats (Kenney MJ and Fels RJ. Am J Physiol Regul Integr Comp Physiol 283: R513-R520, 2002). Central mechanisms by which aging alters visceral SND responses to heating are unknown. We tested the hypothesis that forebrain neural circuits are involved in suppressing sympathoexcitatory responses to heating in chloralose-anesthetized, senescent F344 rats. Renal and splanchnic SND responses to increased (38°C-41°C) internal temperature were determined in midbrain-transected (MT) and sham-MT young (3-mo-old), mature (12-mo-old), and senescent (24-mo-old) F344 rats and in cervical-transected (CT) and sham-CT senescent rats. Renal SND remained unchanged during heating in MT and sham-MT senescent rats but was increased in CT senescent rats. Splanchnic SND responses to heating were higher in MT vs. sham-MT senescent rats and in CT vs. MT senescent rats. SND responses to heating were similar in MT and sham-MT young and mature rats. Mean arterial pressure (MAP) was increased during heating in MT but not in sham-MT senescent rats, whereas heating-induced increases in MAP were higher in sham-MT vs. MT young rats. These data suggest that in senescent rats suppression of splanchnic SND to heating involves forebrain and brain stem neural circuits, whereas renal suppression is mediated solely by brain stem neural circuits. These results support the concept that aging alters the functional organization of pathways regulating SND and arterial blood pressure responses to acute heating.

sympathetic nerve discharge; sympathetic nerve activity; decerebration; Fischer 344 rats

CHANGING THE LEVEL OF EFFERENT sympathetic nerve activity in response to environmental stress is an important means by which mammals maintain physiological homeostasis. Hyperthermia produced by acute heat stress prominently alters sympathetic nerve outflow. Acute heating increases muscle sympathetic nerve activity in conscious humans (8, 31), splanchnic sympathetic nerve discharge (SND) in conscious rats (22), and renal, splanchnic, splenic, and lumbar SND in anesthetized rats (12, 16-18, 20) and decreases sympathetic nerve activity directed to the caudal ventral artery in the rat (15). In addition, moderate body warming decreases skin sympathetic nerve activity in human subjects (10). Heating-induced sympathoexcitatory responses play a critical role in mediating cardiovascular responses to increased internal body temperature (Tc) (17, 21, 23). For example; increases in mesenteric resistance in response to elevations in Tc are eliminated after celiac ganglionectomy (21), reduced splanchnic vasoconstriction contributes to cardiovascular alterations in heat stroke (23), and blockade of autonomic ganglionic transmission during hyperthermia reduces mean arterial pressure (MAP) to values less than those produced by ganglionic blockade at normothermia (17), suggesting that sympathetic activation is important for counteracting vasodilatory influences during acute heating.

Aging alters cardiovascular responses to heating in human subjects (2, 28). In a comprehensive study, Minson et al. (28) reported reduced cardiac output and stroke volume, attenuated cardiac inotropic function, reduced skin blood flow, and less redistribution of blood flow from the splanchnic and renal circulations during heating in older compared with young men. One implication of these results is that sympathetic nerve responses to direct passive heating may be attenuated in aged compared with young men; however, no measure of sympathetic nerve activity was completed in this study. Using an animal model of aging, Kenney and Fels (18) reported that directly recorded renal and splanchnic SND responses to heating are significantly reduced in senescent compared with young Fischer 344 (F344) rats. In addition, renal SND responses to heating in mature (12-mo-old) F344 rats are higher than those in senescent rats (18). The attenuated SND responses to heating in senescent rats are not the result of a generalized inability of these animals to activate thermoregulatory effectors or increase SND in response to acute stress and are not due to baroreceptor reflex inhibition of efferent SND (18). Together, these results suggest that aging alters the responsiveness of central sympathetic neural circuits to acute heat stress in F344 rats.

An important unresolved issue concerns what level(s) of the neuraxis is involved in suppressing SND responses to heat stress in senescent rats. At least two lines of evidence suggest that forebrain neural circuits may play a role. First, Cox et al. (7) reported that, compared with young rats, senescent rats demonstrate increased internal and decreased tail temperatures in response to acute heat stress. These investigators proposed that changes in hypothalamic (i.e., forebrain) pathways might contribute to the altered thermoregulatory responses observed in senescent rats (7). Second, Kenney et al. (19) observed that renal SND responses to heating are significantly attenuated in heart failure compared with sham heart failure rats, similar to differences in SND responses to heating in senescent compared with young F344 rats. After ibotenic acid-induced lesions of the paraventricular nucleus, heart failure and sham heart failure rats demonstrate similar renal sympathoexcitatory responses to heating, suggesting that forebrain neural circuits play a role in suppressing renal SND responses to hyperthermia in heart failure rats (19). Whether this is the case in senescent F344 rats remains to be determined.

In the present study, we tested the hypothesis that forebrain neural circuits are involved in suppressing renal and splanchnic SND responses to heating in senescent F344 rats. We predicted that surgical disconnection of forebrain and brain stem neural circuits (i.e., midbrain transection) would remove a forebrain-mediated inhibition, thereby augmenting SND responses to heating in senescent F344 rats. In contrast, and on the basis of the results of our laboratory's recent study (20) demonstrating similar SND responses to heating in midbrain-transected (MT) and sham-MT young Sprague-Dawley rats, we predicted that midbrain transections would have little or no effect on SND responses to heating in young and mature F344 rats. These findings would support the idea that forebrain neural circuits are involved in suppressing SND responses to heat stress in senescent F344 rats.

Contrary to our original hypothesis, the present results demonstrate that renal SND remained unchanged during heating in MT and sham-MT senescent rats and splanchnic SND responses to heating in MT senescent rats were less than those in MT young and mature rats, supporting a role for brain stem neural circuits in suppressing SND responses to heat stress in senescent F344 rats. On the basis of these findings, we hypothesized that, after cervical spinal transection, spinal systems, in the absence of supraspinal neural circuits, may be capable of generating potent sympathoexcitatory responses to acute heat stress in senescent F344 rats. To test this hypothesis, we determined renal and splanchnic SND responses to heating in cervical-transected (CT, first cervical vertebra) and sham-CT senescent rats.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 DISCLOSURES
 ACKNOWLEDGMENTS
 REFERENCES
 
General procedures. The Institutional Animal Care and Use Committee approved the experimental procedures and protocols used in the present study, and all procedures were performed in accordance with the American Physiological Society's guiding principles for research involving animals (1). Experiments were performed on young (3.3 ± 0.2-mo-old, 283 ± 9 g, n = 16), mature (12.6 ± 0.1-mo-old, 394 ± 10 g, n = 18), and senescent (24 ± 0.3-mo-old, 406 ± 6 g, n = 21) F344 rats. Anesthesia was induced (3% induction) and surgical procedures were completed (1.5-2.5%) by using isoflurane. A catheter was placed in the femoral vein for administration of {alpha}-chloralose (50 mg/kg initial dose; 35-50 mg·kg-1·h-1 maintenance dose) during the heating intervention (16-20). The trachea was cannulated with a polyethylene-240 catheter. Femoral arterial pressure was monitored by using a pressure transducer that was connected to a blood pressure analyzer. Heart rate (HR) was derived from the pulsatile arterial pressure output of the blood pressure analyzer. Colonic temperature was measured with a thermistor probe inserted ~5 cm into the colon. Tc was maintained between 37.8°C and 38.0°C during surgical procedures by a homeothermic blanket.

Neural recordings. Activity was recorded biphasically (band pass 30-3,000 Hz) with a platinum bipolar electrode from renal and splanchnic sympathetic nerves. Sympathetic nerves were isolated by using a lateral approach. The nerve-electrode preparations were covered with silicone gel, and sympathetic nerve activity was full-wave rectified and integrated (time constant, 10 ms). For monitoring during the experiment and for subsequent data analysis, the filtered neurogram was routed to an oscilloscope and a nerve traffic analyzer. The level of activity was quantified as volts times seconds, and SND recordings were corrected for background noise after administration of the ganglionic blocker trimethaphan camsylate (10 mg/kg iv) or nerve crush (16-20).

Midbrain transection. Isoflurane-anesthetized rats were placed in a stereotaxic apparatus. Following removal of a portion of the skull, midbrain transections were completed by performing sequential left and right hemisections at the level of the superior colliculus (20). Transections were completed through the rostral portion of the superior colliculus. The level of transection was verified by gross examination of the brain stem and by evaluation of sagittal sections (40-µm thickness) stained with cresyl violet. Sham transections were completed by removing similar portions of the skull without completion of the surgical hemisections.

Cervical spinal cord transection. Isoflurane-anesthetized rats were placed in a stereotaxic apparatus, and a laminectomy was performed to expose the spinal cord. Following removal of the dura, mineral oil was applied to the exposed spinal cord to keep it moist. The spinal cord was transected at the level of the first cervical vertebra (20). Sham transections involved completing a laminectomy to expose the spinal cord without completing the subsequent surgical transection of the spinal cord. Spinal cord transection was verified at the end of each experiment by dissection at the lesion site.

Experimental protocols. Following completion of the initial surgical procedures (e.g., arterial and venous cannulations, isolation of sympathetic nerves, etc.), the anesthetized rats were allowed to stabilize for 30 min (pretransection control) before completion of surgical transections (midbrain or spinal cord) or sham transections (midbrain or spinal cord). Midbrain and spinal cord transections (or the related sham transections) were completed at the end of the pretransection control period. The animals were allowed to recover for up to 90 min after the surgical and sham transactions (posttransection recovery). Tc was maintained at 38°C during the pretransection control and posttransection recovery periods. At the end of the posttransection recovery period, Tc was increased at a rate of 0.1°C/min from 38 to 41.0°C by using a heat lamp (16-20). The heating protocol was completed in both transected and sham-transected rats. SND responses to heating were determined in young (simultaneous renal-splanchnic recordings, n = 6; single splanchnic recording, n = 1; single renal recordings, n = 3), mature (simultaneous renal-splanchnic recordings, n = 9; single splanchnic recordings, n = 2), and senescent (simultaneous renal-splanchnic recordings, n = 5; single renal recording, n = 1) MT rats; young (simultaneous renal-splanchnic recordings, n = 6), mature (simultaneous renal-splanchnic recordings, n = 5; single splanchnic recordings, n = 2), and senescent (simultaneous renal-splanchnic recordings, n = 5; single renal recordings, n = 2) sham-MT rats; senescent (simultaneous renal-splanchnic recordings, n = 4; single splanchnic recordings, n = 1) CT rats; and senescent (simultaneous renal-splanchnic recordings n = 2; single splanchnic recording, n = 1) sham-CT rats.

Data included in the manuscript (MAP, HR, and the level of activity in the renal and splanchnic nerves) were obtained at the following experimental times: 1) during the pretransection control period (referred to as Pre in Figs. 1, 2, 3, 4), 2) during the posttransection recovery period (referred to as Post in Figs. 1, 2, 3, 4), and 3) during the heating protocol at 39, 39.5, 40, 40.5, and 41°C Tc. Percent changes in renal and splanchnic SND during heating were calculated from levels recorded during the pretransection period.



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  		Fig. 1. Renal (left) and splanchnic (right) sympathetic nerve discharge (SND) during pretransection control (Pre), posttransection recovery (Post), and progressive increases in internal body temperature (Tc; 39, 39.5, 40, 40.5, and 41.0°C) in young (A), mature (B), and senescent (C) midbrain-transected (MT, {circ}) and sham midbrain-transected (sham-MT, {blacksquare}) Fischer 344 (F344) rats. *P < 0.05 vs. Post. {dagger}P < 0.05 vs. sham-MT rats.

 


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  		Fig. 2. Mean arterial pressure (MAP) during pretransection control, posttransection recovery, and progressive increases in Tc (39, 39.5, 40, 40.5, and 41.0°C) in young (A), mature (B), and senescent (C) MT ({circ}) and sham-MT ({blacksquare}) F344 rats. *P < 0.05 vs. Post. **P < 0.05 vs. Pre. {dagger}P < 0.05 vs. sham-MT rats.

 


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  		Fig. 3. Heart rate (HR) during pretransection control, posttransection recovery, and progressive increases in Tc (39, 39.5, 40, 40.5, and 41.0°C) in young (A), mature (B), and senescent (C) MT ({circ}) and sham-MT ({blacksquare}) F344 rats. bpm, Beats per minute. *P < 0.05 vs. Post. {dagger}P < 0.05 vs. sham-MT rats.

 


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  		Fig. 4. Renal and splanchnic SND (A), MAP (B), and HR (C) during pretransection control, posttransection recovery, and progressive increases in Tc (39, 39.5, 40, 40.5, and 41.0°C) in cervical-transected (CT) and sham cervical-transected (sham-CT) senescent F344 rats. A: {triangleup}, CT-splanchnic; {circ}, CT-renal; {blacksquare}, sham-CT with renal and splanchnic SND combined. B and C: {circ}, CT; {blacksquare}, sham-CT. *P < 0.05 vs. Post. {dagger}P < 0.05 vs. sham-CT rats.

 

Data analysis. Values in the text and figures are means ± SE. Results were analyzed by using analysis of variance techniques with a repeated-measures design followed by Bonferroni post hoc tests. P < 0.05 indicated statistical significance. SND, MAP, and HR responses to heating were analyzed with respect to values recorded during the posttransection period.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 DISCLOSURES
 ACKNOWLEDGMENTS
 REFERENCES
 
Renal (Fig. 1, left) and splanchnic (Fig. 1, right) SND were not significantly altered after midbrain transection or sham midbrain transections in young (Fig. 1A), mature (Fig. 1B), and senescent (Fig. 1C) F344 rats (compare Pre with Post values). Renal and splanchnic SND were significantly increased during heating in MT and sham-MT young and mature rats, and SND responses to heating did not differ between MT and sham-MT young rats or between MT and sham-MT mature rats. Renal SND remained unchanged during heating in MT and sham-MT senescent rats, and responses to heating did not differ between groups (with the exception of 39°C). Splanchnic SND was significantly increased during heating in MT but not in sham-MT senescent rats, and responses to heating were significantly higher in MT compared with sham-MT senescent rats.

MAP was significantly reduced after midbrain transections in young and senescent F344 rats but remained unchanged after sham midbrain transections in young (Fig. 2A), mature (Fig. 2B), and senescent (Fig. 2C) F344 rats (compare Pre with Post values). MAP in sham-MT rats was significantly increased during heating in young and mature but not in senescent rats. MAP in MT rats remained unchanged during heating in young and mature rats but was significantly increased during heating in senescent rats. MAP responses to heating were significantly higher in sham-MT compared with MT young rats, did not differ between sham-MT and MT mature rats, and were significantly higher at 41°C in MT compared with sham-MT senescent rats.

Midbrain and sham midbrain transections did not significantly alter the level of HR in young (Fig. 3A), mature (Fig. 3B), and senescent (Fig. 3C) F344 rats (compare Pre with Post values). HR was significantly increased during heating in MT and sham-MT young, mature, and senescent rats. Heating-induced increases in HR were significantly higher in MT compared with sham-MT senescent rats.

SND was not significantly changed after cervical or sham cervical transections in senescent rats (compare Pre with Post values in Fig. 4A). SND (renal and splanchnic) was significantly increased during heating in CT and sham-CT senescent rats, although responses were significantly higher in CT rats (Fig. 4A). Renal and splanchnic SND data shown in Fig. 4A were combined for sham-CT experiments because of similar responses in these nerves (e.g., at 41°C, renal SND = 31 ± 9% and splanchnic SND = 34 ± 9%). Also, renal and splanchnic SND responses to heating at 41°C were significantly higher in senescent CT compared with senescent MT rats (Fig. 5).



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  		Fig. 5. Changes in renal (left) and splanchnic (right) SND after heating to 41°C in MT (renal, n = 6; splanchnic, n = 5) and CT (renal, n = 4; splanchnic, n = 5) senescent F344 rats. *P < 0.05 vs. MT senescent F344 rats.

 

MAP tended to be reduced (Pre, 84 ± 7 mmHg; Post, 67 ± 9 mmHg; P < 0.09) but not significantly so from baseline levels after cervical transections and remained unchanged after sham cervical transections in senescent rats (compare Pre with Post values in Fig. 4B). MAP remained unchanged during heating in CT and sham-CT senescent rats. HR was unchanged from baseline levels in CT and sham-CT senescent rats (compare Pre with Post values in Fig. 4C). HR was progressively and significantly increased during heating in CT and sham-CT senescent rats.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
DISCLOSURES
 ACKNOWLEDGMENTS
 REFERENCES
 
The present results provide experimental support for four findings that contribute to understanding the organization of neural circuits responsible for suppressing SND responses to heating in aged rats. First, hyperthermia significantly increased renal and splanchnic SND in sham-MT young and mature F344 rats but not in sham-MT senescent F344 rats. Second, renal SND remained unchanged during heating in MT senescent rats but was significantly increased during heating in MT young and mature F344 rats. Third (and in contrast to renal SND), splanchnic SND was significantly, yet modestly, increased during heating in MT senescent F344 rats. Hyperthermia produced marked splanchnic sympathoexcitation in MT young and MT mature F344 rats. Fourth, SND (renal and splanchnic) responses to heating were higher in CT compared with sham-CT senescent F344 rats and in CT compared with MT senescent F344 rats. Together, these results suggest that brain stem neural circuits are involved in suppressing renal, and in part splanchnic, SND responses to heating in senescent but not in young F344 rats, supporting the concept that aging alters the functional organization of pathways controlling SND responses to increased Tc.

Direct heating produces splanchnic and renal vasoconstriction in human subjects (37), increases visceral vascular resistance in conscious and anesthetized rats (23), and produces renal (16-18, 20) and splanchnic (12, 16-18, 22) sympathoexcitation in young rats. Splanchnic vasoconstriction during acute heating exerts an important influence on arterial blood pressure regulation in the face of intense cutaneous vasodilation in human subjects (37), and reduced splanchnic vasoconstriction contributes to cardiovascular alterations in heat stroke (23). Several lines of evidence support the idea that aging alters visceral organ blood flow and sympathetic nerve responses to acute heat stress. Renal blood flow is reduced during heating in mature but not in senescent F344 rats (38), the blood flow redistribution profile to heating is altered in older compared with young men (28), hyperthermia alters the SND bursting pattern in young but not in senescent F344 rats (18), and renal and splanchnic SND responses to heating are attenuated in young compared with senescent F344 rats (18). Although age-related alterations in SND regulation may contribute to changes in the ability of senescent mammals to respond to acute heating, central neural mechanisms mediating the attenuated SND responses to heating in senescent rats are not known.

Central sympathetic neural circuits are located at multiple levels of the neuraxis, including forebrain, brain stem, and spinal sites (3, 4, 9, 26, 39). These circuits and their interconnections constitute a complex neural network regulating efferent SND. Because of the inherent complexity in the central regulation of efferent SND and the lack of information examining the effect of age on central sympathetic nerve regulation, we chose to use midbrain and spinal cord transections as an experimental strategy to provide information about the rostrocaudal extent of central neural areas required for mediating SND responses to acute heating in senescent rats. Previous studies have used transection procedures to study central neural components involved in mediating a variety of different physiological responses, including vasomotor changes to thermal stimulation of the medulla and spinal cord (6), cardiovascular responses to diving (11), sympathoexcitation to hypoxia (40), inhibition of baroreflex vagal bradycardia (32), shock-induced antinociception (27), heat production and heat loss mechanisms to capsaicin administration (34), and skeletal muscle rigidity (33).

The findings that renal SND responses to heating in senescent rats were similar in MT compared with sham-MT rats and higher in CT compared with MT rats suggest a critical role for brain stem neural circuits in suppressing renal SND responses to increased Tc in aged F344 rats. Because much is known about the medullary neurocircuitry regulating efferent sympathetic nerve outflow, the present results provide experimental direction for the design of future studies to identify central mechanisms responsible for suppressing renal SND responses to heating in senescent rats. The degree of sympathoexcitation or sympathoinhibition generated by brain stem neural circuits is primarily mediated by changing the level of neuronal excitation in the rostral ventrolateral medulla (RVLM) (14, 25, 29, 36). An important neurotransmitter responsible for inhibition in the RVLM is GABA (4, 24). It is tempting to speculate that the suppression of renal, and in part splanchnic, SND responses to heating in senescent rats may result from increased GABAergic inhibition of sympathetic premotor neurons in the RVLM. In contrast to renal SND, the present findings suggest a role for both forebrain and brain stem neural circuits in suppressing splanchnic SND responses to increased Tc in aged F344 rats. As reviewed by Morrison (30), a hierarchical organization of differential sympathetic regulation exists in the central nervous system, and the present results suggest that this organizational structure is present in aged rats during acute heat stress, although the operating principles underlying this organization remain to be determined.

MAP responses to heating were significantly reduced in MT compared with sham-MT young F344 rats, despite similar SND (renal and splanchnic) and HR responses to heating. One possible explanation for this finding is that increases in MAP to heating in young rats with an intact neuraxis may be mediated by a combination of brain stem-dependent sympathetic and forebrain-dependent nonsympathetic components (e.g., vasopressin, angiotensin II). Therefore, despite similar heating-induced increases in SND (renal and splanchnic) in MT and sham-MT rats, the loss of the forebrain-dependent nonsympathetic component to arterial blood pressure regulation after midbrain transection would result in an attenuated MAP response to heating in young rats. This seems to be an unlikely explanation because ganglionic blockade during hyperthermia decreases MAP from 177 ± 6 to 51 ± 3 mmHg in young rats with an intact neuraxis (17), demonstrating that the sympathetic nervous system is the primary effector in regulation of MAP during increased Tc in these animals. Because a hierarchical organization of differential sympathetic regulation exists in central neural circuits (30), an alternative explanation may be that heating-induced increases in the level of activity in sympathetic nerves other than those innervating splanchnic and renal targets are dependent on forebrain neural circuits. If this were the case, then the overall sympathoexcitation to heating would be reduced in MT young F344 rats, thereby contributing to the attenuated MAP responses to heating in these animals. Additional studies are required to determine if this is the case. In contrast to young F344 rats, MAP was significantly increased during heating in MT but not in sham-MT senescent F344 rats. The enhanced splanchnic SND and HR responses to heating in MT senescent rats likely contributed to the heating-induced pressor response; however, the substantial increase in MAP during heating (40 mmHg from control at a Tc of 41°C) in these animals seems disproportionately high when considering that during heating renal SND remained unchanged, splanchnic SND was significantly but modestly increased (59% at 41°C compared with a 134% increase in splanchnic SND at 41°C in young F344 rats), and HR responses were similar to those observed in young F344 rats. Although additional studies are required to provide mechanistic insight into arterial blood pressure regulation during heating in decerebrate young and senescent F344 rats, the present findings suggest that the forebrain influence on arterial blood pressure regulation in response to acute heating is different in young and senescent F344 rats.

In the present study, the level of renal and splanchnic SND remained unchanged from control after midbrain transections in young, mature, and senescent F344 rats, suggesting that removal of forebrain neural circuits had no effect on basal levels of SND. However, because baroreceptor-innervated rats were used in the present experiments and because midbrain transection reduced MAP in young and senescent rats, it may be that a component of the posttransection level of renal and splanchnic SND was mediated through baroreflex mechanisms, secondary to unloading of the arterial baroreceptors. Acute spinal transection in rats decreases arterial pressure (20, 35, 41) and has been shown to either significantly increase renal and splenogastric nerve activity (35, 41) or to have no effect on the level of renal and splenic nerve activity (Ref. 20 and the present study), indicating that spinal systems are capable of maintaining activity in regionally selective nerves following cervical spinal transection. In addition, spinal cord heating in decerebrate rabbits increases splanchnic and cardiac SND and reduces vasoconstrictor tone in the skin (13), and acute heating in chloralose-anesthetized, decerebrate young Sprague-Dawley rats increases renal and splenic SND, MAP, and HR (20), suggesting that sympathetic nerve responses to heating can be elicited in the absence of supraspinal neural circuits.

Cervical transection experiments were not completed in young and mature F344 rats for the following reasons. First, renal and splanchnic sympathoexcitatory responses to heating were similar in MT and sham-MT young F344 rats and in MT and sham-MT mature F344 rats. Second, SND responses to heating in young and mature F344 rats were similar to those observed during heating in intact and MT young Sprague-Dawley rats (20). Third, hyperthermia-induced renal sympathoexcitatory responses are observed after CT in young Sprague-Dawley rats (20); however, responses are attenuated (not augmented like those observed in the senescent F344 rats in the present study) compared with sham-CT and MT young Sprague-Dawley rats.

One potential limitation of the present study is that anesthesia may negatively influence SND responses to heating. Although this possibility cannot be discounted, the potential adverse influence of anesthesia does not appear to be substantial because acute heating increases SND in conscious humans (8, 31), conscious rats (22), and young, chloralose-anesthetized rats (Refs. 12, 16-18, 20 and the present study). In addition, SND remains unchanged from control during increased Tc in conscious (38) and chloralose-anesthetized (Ref. 18 and the present study) senescent F344 rats, suggesting that the reduced responsiveness of sympathetic neural circuits to heating in senescent rats is not the result of age-associated changes in the sensitivity to chloralose anesthesia. The hyperthermia-induced increase in MAP (17 ± 7 mmHg at 41°C Tc) in the chloralose-anesthetized, sham-MT senescent F344 rats in the present study is similar to the increase in MAP observed during heating in conscious senescent F344 rats (~20 mmHg at 41°CTc) (38). Finally, effector responses to increased Tc can be altered by behavioral modifications (5); therefore, we have chosen to study SND regulation to heating in anesthetized rats to eliminate this influence.


   DISCLOSURES
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 DISCLOSURES
ACKNOWLEDGMENTS
 REFERENCES
 
National Heart, Lung, and Blood Institute Grant HL-69755 supported this research.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 DISCLOSURES
 ACKNOWLEDGMENTS
REFERENCES
 
We thank Jessica Perry for technical assistance.


   FOOTNOTES
 

Address for reprint requests and other correspondence: M. J. Kenney, Dept. of Anatomy and Physiology, Coles Hall, Rm. 228, Kansas State Univ., 1600 Denison Ave., Manhattan, KS 66506 (E-mail: Kenny{at}vet.ksu.edu).

Original submission in response to a call for papers on "Physiology of Aging."

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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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 DISCLOSURES
 ACKNOWLEDGMENTS
 REFERENCES
 

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