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Am J Physiol Regul Integr Comp Physiol 295: R727-R732, 2008. First published May 28, 2008; doi:10.1152/ajpregu.00144.2008
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Physiological and Molecular Mechanisms Implicated in the Neural Control of Circulation

Influence of sedentary versus physically active conditions on regulation of plasma renin activity and vasopressin

Patrick J. Mueller

Dalton Cardiovascular Research Center and Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, Missouri; and Department of Physiology, Wayne State University, School of Medicine, Detroit, Michigan

Submitted 27 February 2008 ; accepted in final form 27 May 2008


   ABSTRACT
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Physical inactivity is an independent risk factor for cardiovascular disease. Sedentary animals compared to physically active controls exhibit enhanced sympathoexcitatory responses, including arterial baroreflex-mediated sympathoexcitation. Hypotension-induced sympathoexcitation is also associated with the release of vasoactive hormones. We hypothesized that sedentary conditions may enhance release of the vasoactive hormones AVP and ANG II. To test this hypothesis, the humoral response to hypotension was examined in conscious rats after 9–12 wk of sedentary conditions or "normally active" conditions. Normally active conditions were produced by allowing rats access to running wheels in their home cages. Running distance peaked after 4 wk (4.5 ± 0.7 km/day), and the total distance run after 9 wk was 174 ± 23 km (n = 25). Similar levels of hypotension were induced in conscious sedentary or physically active animals with the arterial vasodilator, diazoxide (25 mg/kg iv). Control experiments used a saline injection of equivalent volume. Plasma samples were collected and assayed for plasma AVP concentration and plasma renin activity (PRA). Sedentary conditions significantly enhanced resting and hypotension-induced PRA relative to normal physical activity. In contrast, resting and hypotension-induced AVP levels were not statistically different between groups. These data suggest that baroreflex-mediated activation of the renin-angiotensin system, but not AVP secretion, is enhanced by sedentary conditions. We speculate that augmented activation of the renin-angiotensin system may be related to enhanced sympathetic outflow observed in sedentary animals and may contribute to increased risk of cardiovascular disease in the sedentary population.

physical activity; physical inactivity; neurohumoral control; angiotensin II

PHYSICAL INACTIVITY IS A MAJOR risk factor for cardiovascular disease (50) and despite significant advances in treatment options, cardiovascular disease remains the leading cause of death in the United States (39). These disturbing trends coincide strongly with the growing rates of physical inactivity in the general population (30). Physical inactivity along with poor diet has been predicted from data by the Centers for Disease Control to surpass tobacco as primary contributing factors to premature death in the United States (30). It is critical then to delineate the mechanisms by which a sedentary lifestyle contributes to cardiovascular disease.

Previous studies have reported that sedentary animals exhibit enhanced levels of sympathetic nervous system activity in response to baroreceptor unloading compared with animals in which physical activity was maintained by treadmill exercise or spontaneous wheel running (6, 13, 36). In addition to sympathoexcitation, the response to baroreceptor unloading is also associated with activation of the renin-angiotensin system and increased plasma concentrations of vasoactive hormones such as angiotensin and AVP (35, 42, 47, 48). It is possible that regulation of the renin-angiotensin system or vasopressin secretion is altered by physical activity or inactivity. For example, regulation of AVP has been reported to be altered in sedentary compared with endurance-trained subjects (8, 17). In addition, we previously reported differential effects of hindlimb unloading on baroreflex-mediated sympathoexcitation, activation of the renin-angiotensin system, and vasopressin secretion (29, 35). Therefore, on the basis of the previous observations that sedentary vs. physically active conditions enhance baroreflex-mediated sympathoexcitation (6, 13, 36), we hypothesized that regulation of the renin-angiotensin system and AVP secretion would be enhanced in sedentary vs. physically active rats. To test this hypothesis, we examined regulation of plasma AVP levels and plasma renin activity (PRA) in rats that had sedentary conditions imposed on them or were allowed to be "normally" physically active by the provision of running wheels in their home cage.


   METHODS
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 METHODS
RESULTS
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All procedures were approved by the Animal Care and Use Committee of the University of Missouri-Columbia and conducted in accordance with the American Physiological Society's Guiding Principles in the Care and Use of Animals. All animals received food (Formulab Diet, 0.28% sodium; Purina, St. Louis, MO) and tap water ad libitum.

Daily spontaneous running. Fifty-four male Sprague-Dawley rats weighing 75–100 g at a time of arrival in the vivarium were used for these studies. Animals were housed individually in standard cages outfitted with custom-made running wheels (physically active group, n = 25) or without running wheels (sedentary group, n = 29) for 9–12 wk. Daily running distances, cumulative running distances, average running time, and average running speed were recorded daily with the use of bicycle computers (Sigma Sport, Olney, IL) calibrated to the diameter of the running wheel.

Surgical instrumentation. Two days prior to experimentation, animals were instrumented under halothane anesthesia and aseptic conditions with femoral arterial and venous catheters [polyethylene (PE)-50 fused to PE-10] to record mean arterial pressure (MAP) and heart rate (HR) and for intravenous injection, respectively, similar to our previous study (35). Catheters were tunneled under the skin and exteriorized between the scapulae. Following surgery, catheters were flushed with heparinized saline (10 U/ml) and capped with sterile plugs. Each animal was given subcutaneous fluids (10 ml, 0.9% saline) and returned to its home cage for recovery. Wheels were removed from the cages of physically active animals just prior to surgery. This was done to reduce the effects of an acute bout of exercise on AVP and ANG II levels (51, 53). Animals remained in the experiment room during the 2-day recovery period to acclimate to the experimental surroundings.

Hemodynamic experiments. On the day of experimentation, arterial and venous catheters were connected, and conscious animals were allowed at least 1 h to stabilize in their home cage. Food and water were removed during the experiment. Arterial pressure was monitored from the femoral arterial line via a pressure transducer placed at the level of the heart. MAP and HR were derived electronically using a Powerlab data acquisition system (ADInstruments, Colorado Springs, CO). MAP and HR were monitored to ensure stable baselines once the experiment began. A minimum of 10 min of resting data was obtained prior to the long-acting vasodilator diazoxide (25 mg/kg, Hyperstat, 15 mg/ml, Schering Plough, Kenilworth, NJ), or an equivalent volume of saline (0.9%). Diazoxide was used as a hypotensive agent based on previous studies from our laboratory and others that have reported that it elicits a steady-state hypotension and produces significant increases in vasopressin concentration (35) and PRA (35, 47, 48) in conscious rats. In addition, diazoxide has been shown to produce selective arterial vasodilation (14) without affecting plasma osmolality (14, 48) or central venous pressure (14).

Previous studies have reported that plasma vasopressin and renin activity peak after 10–30 min of sustained hypotension (47, 48). Therefore, similar to our previous study (35), hypotension was induced for 20 min, after which animals were anesthetized quickly by a rapid intravenous injection of Inactin (0.3 ml, 100 mg/ml; Sigma-Aldrich, St. Louis, MO). Animals were removed promptly from their cage and decapitated. As before (35), decapitation was judged to be the fastest and most humane method to obtain the necessary size blood sample (4.4 ml) that was required for both PRA (0.2 ml) and plasma vasopressin (4 ml) assays.

Blood samples were obtained from trunk blood and collected into chilled centrifuge tubes containing ~10 µl/ml EGTA (15%). A small portion of this sample was used to determine hematocrit in each animal. The plasma remaining in the hematocrit sample was used to assess plasma protein concentration with a clinical refractometer. The remainder of the blood sample was centrifuged at 5000 g for 10 min in a refrigerated centrifuge (internal temperature <4°C). Plasma was removed from the blood sample and was aliquoted into individual sample tubes, which were stored at –70°C. Plasma samples were shipped on dry ice to the University of Iowa General Clinical Research Center (GCRC) Analytical Laboratory and assayed for vasopressin and renin activity on a fee basis similar to a previous study (35). Briefly, plasma vasopressin concentrations were measured by specific RIA with a sensitivity of 0.170 pg/ml and average intra-assay and inter-assay coefficients of variation of 11% and 17%, respectively (27). The vasopressin antibody was donated by Dr. Willis K. Samson at St. Louis University and shows less than 0.1% cross-reactivity with oxytocin, ANG I, ANG II, corticotrophin-releasing factor, and atrial natriuretic factor (41). PRA was measured as the generation of ANG II by an ANG I (125-I) RIA kit (NEN Life Science Product, PerkinElmer Life Sciences, Boston, MA), as used in our previous study (35). Intra-assay and inter-assay coefficients of variation averaged 8% and 10%, respectively, and the sensitivity of the method is 0.1 ng/ml/h.

Data collection and analysis. Arterial pressure, MAP, and HR were acquired online at 1,000 samples/s using a computer-based data acquisition system (PowerLab, ADInstruments, Colorado Springs, CO). Data comparing levels of MAP, HR, vasopressin, and PRA with diazoxide or saline injections were analyzed by two-way ANOVA with repeated measures where appropriate. Plasma vasopressin values were log transformed to correct for nonnormal distribution before being analyzed by ANOVA. PRA values were also similarly transformed. When ANOVA indicated a significant interaction, differences between individual means were analyzed by Holm-Sidak method (SigmaStat for Windows ver. 3.5, Systat, Point Richmond, CA). The Student's t-test was used to determine group differences in body weight, hematocrit, plasma protein, and resting hemodynamics. A probability of P < 0.05 was considered statistically significant. Data are expressed as means ± SE.


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Running wheel distances. Figure 1 demonstrates weekly distances run by rats provided with running wheels over the first 9 wk. Animals progressively increased their running distance over the first 5 wk and then exhibited a small decline from this peak until the day of experimentation. On a daily basis, running distance peaked between the 4th and 5th wk (day 32, 4.6 ± 0.7 km/day) and was associated with peak average running time during this same week (day 31, 1:46:04 ± 13:26). Average running speed varied over time from 29 ± 1 m/min (day 1) to 41 ± 1 m/min (five different days).


Figure 1
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  		Fig. 1. Daily distances for rats provided with running wheels over 9 wk. On average, running distance peaked between the 4th and 5th wk (day 32, 4.6 ± 0.7 km/day).

 
Effects of sedentary conditions vs. physical activity. Table 1 contains data regarding the effects of 9–12 wk of sedentary conditions compared with physical activity. As expected, physically active rats weighed significantly less than sedentary rats. Prior to injection of saline or diazoxide, resting mean arterial pressure appeared lower in physically active animals, but this effect did not reach significance (P = 0.212). In addition, resting heart rates were similar between physically active and sedentary rats immediately prior to injection of saline or diazoxide. Plasma samples for hematocrit and plasma protein were not influenced by injections of diazoxide relative to injections of saline whether analyzed by t-test (combining sedentary and physically active groups) or by 2 way ANOVA (separating sedentary and physically active groups; P > 0.05 for both tests). As shown in Table 1, hematocrits did not differ between physically active and sedentary rats, but there was a trend for a small, relative decrease in plasma protein in physically active rats (P = 0.06, t-test).


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  		Table 1. Baseline effects of 8 wk of physical activity vs. sedentary conditions

 
Hemodynamic responses. Figure 2 demonstrates AP and HR responses to intravenous diazoxide (25 mg/kg) or equivalent volumes of saline (0.9%) in sedentary or physically active rats. Injection of saline produced no significant effect on MAP in either group. Saline injection did produce a small, but significant, increase in HR that was similar between groups. In contrast, injection of diazoxide produced a rapid and sustained decrease in MAP that was significantly different from saline. Importantly, the hypotension produced by diazoxide was sustained similarly in both groups for the 20-min time period with some slight recovery toward control levels. The hypotensive responses were associated with increases in HR that were equally sustained over the time course and were not significantly different between groups.


Figure 2
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  		Fig. 2. Mean arterial pressure (MAP) and heart rate (HR) responses to the long acting vasodilator diazoxide (25 mg/kg, circles) or saline (SAL, 0.9%, squares) in sedentary controls (solid symbols, dashed lines) or physically active rats produced by daily spontaneous running (open symbols, solid lines). Diazoxide produced a rapid and sustained decrease in MAP and increase in HR that was not different between groups. *P < 0.05 for significant effect of diazoxide vs. saline injection.

 
Regulation of PRA. Figure 3A demonstrates plasma renin activity in physically active and sedentary animals in response to diazoxide (25 mg/kg) or equivalent volumes of saline (0.9%). In saline-treated animals, PRA was very similar to resting PRA reported in previous studies using conscious rats (35, 46–48). In both groups of animals, injection of diazoxide produced a significant increase in PRA compared with saline injection. A significant overall effect of sedentary conditions on PRA indicated that sedentary conditions enhanced PRA under both control conditions and during hypotension with diazoxide (overall effect P < 0.05; interaction P = 0.402).


Figure 3
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  		Fig. 3. Plasma renin activity (PRA) (A) and plasma arginine vasopressin levels (AVP) (B) in physically active (nonhatched bars) and sedentary rats (hatched bars) injected with saline (0.9%, open bars) or diazoxide (25 mg/kg, gray bars). Plasma samples were obtained after 20 min of hypotensive or control conditions. *P < 0.05 for overall significant effect of diazoxide vs. saline injection. {dagger}P < 0.05 for overall effect of sedentary vs. physically active conditions. n values are shown in parentheses.

 
Regulation of plasma vasopressin. Figure 3B depicts the effects of diazoxide or saline on vasopressin concentration in sedentary vs. physically active rats. In saline-treated animals, plasma vasopressin was very similar to resting plasma vasopressin values reported in previous studies using conscious rats (35, 46). In both groups, injection of diazoxide produced a significant increase in plasma vasopressin compared with saline injection. Neither resting nor hypotension-induced vasopressin release appeared to be altered by sedentary conditions (overall effect P = 0.468; interaction P = 0.507).


   DISCUSSION
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 ABSTRACT
 METHODS
 RESULTS
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GRANTS
 REFERENCES
 
The purpose of the present study was to test the hypothesis that imposition of sedentary conditions enhances hypotension-induced activation of the renin-angiotensin system and AVP secretion relative to "normally active" conditions produced by spontaneous wheel running. This hypothesis was based on previous studies that demonstrated that baroreflex-mediated sympathoexcitation is greater in sedentary vs. physically active animals (6, 13, 36). The results of our experiments are consistent with our hypothesis that sedentary conditions produce a relative enhancement of resting and hypotension-induced increases in PRA. However, the data argue against an enhancement of resting and hypotension-induced increases in plasma vasopressin levels. These results suggest that there is an uncoupling between the effects of sedentary vs. physically active conditions on regulation of PRA and vasopressin secretion. Collectively, the results of this study and others (6, 13, 36) suggest that baroreflex-mediated increases in PRA and sympathetic nervous system outflow are enhanced in sedentary animals relative to physically active animals. We speculate that these enhancements contribute importantly to the overall detrimental effects of a sedentary lifestyle on arterial blood pressure regulation and cardiovascular health.

Consistent with our original hypothesis, sedentary conditions produced a relative enhancement of resting and hypotension-induced PRA. Higher PRA could be a result of higher resting and baroreflex-mediated sympathoexcitation observed in sedentary vs. physically active animals (11, 13, 24, 36). Specifically, the activity of renal sympathetic nerves, as assessed by renal norepinephrine turnover in humans (28) or by direct recordings in animals (24, 36), is enhanced in sedentary subjects relative to physically active controls. Although it is well known that renal nerves are responsible, at least in part, for stimulation of renin release from the kidney (12), additional experiments are needed to confirm whether other factors are involved, and whether enhanced renal nerve activity observed in previous studies (24, 28, 36) translates into the functionally related increases in PRA observed in the current study.

The underlying mechanisms by which sedentary conditions enhance, or physically active conditions reduce activation of the renin-angiotensin system are not fully known. In the present study, sedentary rats exhibited a trend for a slightly higher plasma protein content (P = 0.06), which could suggest a slightly lower relative plasma volume. A lower plasma volume alone could result in a higher sympathetic tone and increases in PRA via a relative unloading of volume-sensitive cardiopulmonary receptors (2, 3). However, studies by DiCarlo and colleagues (7, 43) suggest that sedentary conditions vs. physically active conditions produced by spontaneous wheel running have no effect on arterial baroreceptor and cardiopulmonary receptor afferent input. Therefore, alterations in the central nervous system processing of arterial and cardiopulmonary receptor input have been proposed to mediate activity-related changes in arterial baroreflex function (7, 43). In support of this hypothesis, we and others have reported physical activity-dependent changes within brain regions involved in cardiovascular control (33). These changes include alterations in neuronal firing properties (21), differences in neuronal structure and innervation (19, 37), and sensitivity to glutamate microinjections (26, 34). Interestingly, exercise training in rabbits with heart failure reduces components of the central renin-angiotensin system and is associated with reductions in elevation plasma ANG II levels (32). Thus, there is substantial evidence to suggest that physical activity-related synaptic plasticity occurs in central nervous system structures that impact regulation of the sympathetic nervous system and the renin-angiotensin system.

The physiological significance of higher PRA in sedentary animals relative to physically active animals is unknown. Higher PRA could result in a number of cardiovascular alterations associated with a sedentary lifestyle, including hypertension (50). A recent report suggests that elevations in sympathetic nervous system activity and the renin-angiotensin system occur prior to the development of heart failure in a mouse model, despite normal resting arterial pressures during this time (15). Similarly, previous reports suggest that disease states, such as heart failure and certain forms of hypertension, are associated with overactivity of both the sympathetic nervous system and the renin-angiotensin system (38, 52, 54). Physical activity (vs. inactivity) appears to be beneficial in reducing overactivity of the sympathetic nervous system and the renin-angiotensin system in congestive heart failure patients and animals (5, 18, 40). Although the current study was performed on otherwise "healthy" animals, it is intriguing to speculate that a sedentary lifestyle alone, or in combination with other cardiovascular risk factors, predisposes individuals to cardiovascular disease via effects on the sympathetic nervous system and the renin-angiotensin system.

Neither resting nor hypotension-induced vasopressin release was affected by sedentary vs. physically active conditions. This lack of effect was surprising to us and contrary to our hypothesis that vasopressin levels would be enhanced in sedentary animals. Since in our previous study performed in hindlimb-unloaded rats (35), we were able to observe significant differences in vasopressin levels using similar methods, we believe that the hypotensive stimulus used was sufficient enough to observe potential differences in vasopressin secretion. The mechanisms by which vasopressin release is stimulated are multifactorial and are regulated by such factors as decreases in blood pressure or blood volume, increased ANG II, and increases in plasma osmolality (44, 45, 49). Enhanced levels of PRA in sedentary animals would have been predicted to result in a greater level of plasma ANG II, since PRA is strongly correlated with plasma ANG II levels in conscious rats (48). Furthermore, Stern and colleagues (21) reported that magnocellular neurons in the PVN that are associated with vasopressin secretion have greater intrinsic excitability in sedentary vs. treadmill-exercised rats. Nonetheless, the data from the present study argue that these differences do not result in an enhancement of vasopressin secretion.

Limitations. It is possible that obtaining our samples at a single time point and following a brief period of anesthesia reduced our chances of seeing a significant difference in vasopressin between groups. We believe these to be unlikely given the half-life of vasopressin (~7 min in rat) and the extended period of hypotension (20 min) that preceded sample collection. In our previous study, we were able to identify significant differences in vasopressin levels in hindlimb-unloaded rats using similar methods (35). Therefore, although we cannot discount the possibility that there may be physical activity-dependent alterations in the time course of plasma vasopressin levels, we can state that vasopressin levels are not statistically different in sedentary animals compared with physically active animals after 20 min of sustained hypotension.

We did not directly measure plasma volume or plasma osmolality in this study and so cannot completely eliminate alterations in these variables between sedentary and physically active rats as contributing factors. Previous studies have reported that plasma osmolality is unaffected when comparing sedentary and physically active subjects (10, 16). Even if higher plasma osmolalities were associated with the trend for lower plasma volumes in sedentary animals, we would have expected this to enhance resting and hypotension-induced AVP levels. Future studies will be necessary to determine directly whether changes in plasma volume, osmolality or other factors contribute to a lack of effect on vasopressin release.

As mentioned, the significant effects on PRA, but not vasopressin, suggest that there is a disassociation between activity-induced changes in baroreflex-mediated increases in PRA and vasopressin release. Previously, we have demonstrated differential alterations in baroreflex regulation of the renin-angiotensin system and vasopressin release in hindlimb-unloaded rats (35), a model of cardiovascular deconditioning (31). However, in contrast to our current study, we observed that hindlimb unloading enhanced both resting and hypotension-induced levels of vasopressin but had no effect on resting or hypotension-induced increases in PRA. These data suggest collectively that the spectrum of physical activity encompassing cardiovascular deconditioning, sedentary conditions, physically active conditions, and endurance training differentially influences baroreflex control of sympathetic nervous system activity, PRA, and vasopressin.

Summary/conclusions. In summary, sedentary conditions vs. physical activity produced by daily spontaneous running alters neurohumoral regulation of the circulation by enhancing activation of the renin-angiotensin system. In contrast, neither resting nor hypotension-induced vasopressin levels appear to be altered in sedentary compared with physically active rats. Interestingly, these data suggest that resting and baroreceptor reflex control of the renin-angiotensin system, vasopressin secretion, and the sympathetic nervous system are altered differentially by various levels of physical activity and inactivity.

Perspectives and Significance

Although it has been well documented that regular physical activity can lower blood pressure and sympathetic activity in normal and hypertensive humans (4, 20, 39) and animals (1, 9, 22–24, 36), the conclusions of the majority, if not all, of these studies have focused on the role of exercise training rather than the effects of remaining sedentary. This is a subtle, yet important difference in perspective, as a sedentary lifestyle is not only a risk factor for cardiovascular disease but is now considered a chronic disease process that is modifiable by regular exercise (25). It has been suggested recently that physically active or trained subjects should be identified as the control or "normal" group, and the sedentary group should be considered the disease group (25). This is logical from an evolutionary standpoint since human beings have relied on being physically active to maintain their survival for the majority of our existence (25). Thus, the identified "healthy" effects of physical activity may actually be related to the detrimental effects of remaining sedentary. As mentioned, the current study was performed on otherwise "healthy" animals. We speculate that a sedentary lifestyle alone, or in combination with other cardiovascular risk factors, predisposes individuals to cardiovascular disease via effects on the sympathetic nervous system and the renin-angiotensin system.


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This research was supported by grants from the Heartland Affiliate of the American Heart Association (B.G.I.A. # 0265264Z and G.I.A # 0650161Z). This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR-16498 from the National Center for Research Resources, National Institutes of Health.


   ACKNOWLEDGMENTS
 
The author would like to thank Dr. Eileen M. Hasser at the University of Missouri-Columbia for helpful input on this project. I would also like to thank Dr. Hasser and Drs. Noreen F. Rossi and Robert A. Augustyniak at Wayne State University School of Medicine for valuable comments on the manuscript. The author wishes to thank Jodie Smith and Sarah Friskey at the University of Missouri for excellent technical assistance, and Donna Farley and the University of Iowa GCRC Analytical Laboratory for the plasma vasopressin and renin activity analyses. Finally, I wish to acknowledge faculty members at the University of Missouri-Columbia and Wayne State University School of Medicine for their interactive discussion on neurohumoral control of the circulation.


   FOOTNOTES
 

Address for reprint requests and other correspondence: P. J. Mueller, Dept. of Physiology, Wayne State Univ. School of Medicine, 540 E. Canfield, Detroit MI 48201 (e-mail: pmueller{at}med.wayne.edu)

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.


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  1. Beatty JA, Kramer JM, Plowey ED, Waldrop TG. Physical exercise decreases neuronal activity in the posterior hypothalamic area of spontaneously hypertensive rats. J Appl Physiol 98: 572–578, 2005.[Abstract/Free Full Text]
  2. Bishop VS, Hasser EM. Arterial and cardiopulmonary reflex in the regulation of the neurohumoral drive to the circulation. Fed Proc 44: 2377–2381, 1985.[Web of Science][Medline]
  3. Bishop VS, Malliani A, Thoren P. Cardiac mechanoreceptors. In: Handbook of Physiology. The cardiovascular system. Peripheral circulation and organ blood flow, Bethesda, MD: Am. Physiol. Soc., 1983, p. 497–813.
  4. Blumenthal JA, Sherwood A, Gullette ECD, Babyak M, Waugh R, Georgiades A, Craighead LW, Tweedy D, Feinglos M, Appelbaum M, Hayano J, Hinderliter A. Exercise and weight loss reduce blood pressure in men and women with mild hypertension—effects on cardiovascular, metabolic, and hemodynamic functioning. Arch Intern Med 160: 1947–1958, 2000.[Abstract/Free Full Text]
  5. Braith RW, Welsch MA, Feigenbaum MS, Kluess HA, Pepine CJ. Neuroendocrine activation in heart failure is modified by endurance exercise training. J Am Coll Cardiol 34: 1170–1175, 1999.[Abstract/Free Full Text]
  6. Chen CY, DiCarlo SE. Daily exercise and gender influence arterial baroreflex regulation of heart rate and nerve activity. Am J Physiol Heart Circ Physiol 271: H1840–H1848, 1996.[Abstract/Free Full Text]
  7. Chen CY, DiCarlo SE, Scislo TJ. Daily spontaneous running attenuated the central gain of the arterial baroreflex. Am J Physiol Heart Circ Physiol 268: H662–H669, 1995.[Abstract/Free Full Text]
  8. Claybaugh JR, Pendergast DR, Davis JE, Akiba C, Pazik M, Hong SK. Fluid conservation in athletes: responses to water intake, supine posture, and immersion. J Appl Physiol 61: 7–15, 1986.[Abstract/Free Full Text]
  9. Collins HL, Rodenbaugh DW, DiCarlo SE. Daily exercise attenuates the development of arterial blood pressure related cardiovascular risk factors in hypertensive rats. Clin Exp Hypertens 22: 193–202, 2000.[CrossRef][Web of Science][Medline]
  10. Convertino VA, Brock PJ, Keil LC, Bernauer EM, Greenleaf JE. Exercise training-induced hypervolemia: role of plasma albumin, renin, and vasopressin. J Appl Physiol 48: 665–669, 1980.[Abstract/Free Full Text]
  11. De Angelis K, Wichi RB, Jesus WRA, Moreira ED, Morris M, Krieger EM, Irigoyen MC. Exercise training changes autonomic cardiovascular balance in mice. J Appl Physiol 96: 2174–2178, 2004.[Abstract/Free Full Text]
  12. DiBona GF. Neural control of the kidney: functionally specific renal sympathetic nerve fibers. Am J Physiol Regul Integr Comp Physiol 279: R1517–R1524, 2000.[Abstract/Free Full Text]
  13. DiCarlo SE, Bishop VS. Exercise training attenuates baroreflex regulation of nerve activity in rabbits. Am J Physiol Heart Circ Physiol 255: H974–H979, 1988.[Abstract/Free Full Text]
  14. Evered MD. Relationship between thirst and diazoxide-induced hypotension in rats. Am J Physiol Regul Integr Comp Physiol 259: R362–R370, 1990.[Abstract/Free Full Text]
  15. Ferreira JC, Bacurau AV, Evangelista FS, Coelho MA, Oliveira EM, Casarini DE, Krieger JE, Brum PC. The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice. Am J Physiol Regul Integr Comp Physiol 294: R26–R32, 2008.[Abstract/Free Full Text]
  16. Freund BJ, Claybaugh JR, Dice MS, Hashiro GM. Hormonal and vascular fluid responses to maximal exercise in trained and untrained males. J Appl Physiol 63: 669–675, 1987.[Abstract/Free Full Text]
  17. Freund BJ, Claybaugh JR, Hashiro GM, Dice MS. Hormonal and renal responses to water drinking in moderately trained and untrained humans. Am J Physiol Regul Integr Comp Physiol 254: R417–R423, 1988.[Abstract/Free Full Text]
  18. Gao L, Wang W, Liu D, Zucker IH. Exercise training normalizes sympathetic outflow by central antioxidant mechanisms in rabbits with pacing-induced chronic heart failure. Circulation 115: 3095–3102, 2007.[CrossRef][Web of Science][Medline]
  19. Higa-Taniguchi KT, Silva FC, Silva HM, Michelini LC, Stern JE. Exercise training-induced remodeling of paraventricular nucleus (nor)adrenergic innervation in normotensive and hypertensive rats. Am J Physiol Regul Integr Comp Physiol 292: R1717–R1727, 2007.[Abstract/Free Full Text]
  20. Iwasaki KI, Zhang R, Zuckerman JH, Levine BD. Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit? J Appl Physiol 95: 1575–1583, 2003.[Abstract/Free Full Text]
  21. Jackson K, Vieira Silva HM, Zhang W, Michelini LC, Stern JE. Exercise training differentially affects intrinsic excitability of autonomic and neuroendocrine neurons in the hypothalamic paraventricular nucleus. J Neurophysiol 3211–3220, 2005.
  22. Kramer JM, Beatty JA, Little HR, Plowey ED, Waldrop TG. Chronic exercise alters caudal hypothalamic regulation of the cardiovascular system in hypertensive rats. Am J Physiol Regul Integr Comp Physiol 280: R389–R397, 2001.[Abstract/Free Full Text]
  23. Krieger EM, Brum PC, Negrao CE. Influence of exercise training on neurogenic control of blood pressure in spontaneously hypertensive rats. Hypertension 34: 720–723, 1999.[Abstract/Free Full Text]
  24. Krieger EM, Da Silva GJJ, Negrao CE. Effects of exercise training on baroreflex control of the cardiovascular system. Ann NY Acad Sci 940: 338–347, 2001.[Web of Science][Medline]
  25. Lees SJ, Booth FW. Sedentary death syndrome. Can J Appl Physiol 29: 447–460, 2004.[Web of Science][Medline]
  26. Martins-Pinge MC, Becker LK, Garcia MR, Zoccal DB, Neto RV, Basso LS, de Souza HC, Lopes OU. Attenuated pressor responses to amino acids in the rostral ventrolateral medulla after swimming training in conscious rats. Auton Neurosci 122: 21–28, 2005.[CrossRef][Web of Science][Medline]
  27. Matsuguchi H, Schmid PG, Van Orden D, Mark AL. Does vasopressin contribute to salt-induced hypertension in the Dahl strain? Hypertension 3: 174–181, 1981.[Abstract/Free Full Text]
  28. Meredith IT, Friberg P, Jennings GL, Dewar EM, Fazio VA, Lambert GW, Esler MD. Exercise training lowers resting renal but not cardiac sympathetic activity in humans. Hypertension 18: 575–582, 1991.[Abstract/Free Full Text]
  29. Moffitt JA, Foley CM, Schadt JC, Laughlin MH, Hasser EM. Attenuated baroreflex control of sympathetic nerve activity after cardiovascular deconditioning in rats. Am J Physiol Regul Integr Comp Physiol 274: R1397–R1405, 1998.[Abstract/Free Full Text]
  30. Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. JAMA 291: 1238–1245, 2004.[Abstract/Free Full Text]
  31. Morey-Holton ER, Globus RK. Hindlimb unloading rodent model: technical aspects. J Appl Physiol 92: 1367–1377, 2002.[Abstract/Free Full Text]
  32. Mousa TM, Liu D, Cornish KG, Zucker IH. Exercise training enhances baroreflex sensitivity by an angiotensin II-dependent mechanism in chronic heart failure. J Appl Physiol 104: 616–624, 2008.[Abstract/Free Full Text]
  33. Mueller PJ. Exercise training and sympathetic nervous system activity: evidence for physical activity dependent neural plasticity. Clin Exp Pharmacol Physiol 34: 377–384, 2007.[Web of Science][Medline]
  34. Mueller PJ. Exercise training attenuates increases in lumbar sympathetic nerve activity produced by stimulation of the rostral ventrolateral medulla. J Appl Physiol 102: 803–813, 2007.[Abstract/Free Full Text]
  35. Mueller PJ, Sullivan MJ, Grindstaff RR, Cunningham JT, Hasser EM. Regulation of plasma vasopressin and renin activity in conscious hindlimb-unloaded rats. Am J Physiol Regul Integr Comp Physiol 291: R46–R52, 2006.[Abstract/Free Full Text]
  36. Negrao CE, Irigoyen MC, Moreira ED, Brum PC, Freire PM, Krieger EM. Effect of exercise training on RSNA, baroreflex control, and blood pressure responsiveness. Am J Physiol Regul Integr Comp Physiol 265: R365–R370, 1993.[Abstract/Free Full Text]
  37. Nelson AJ, Juraska JM, Musch TI, Iwamoto GA. Neuroplastic adaptations to exercise: neuronal remodeling in cardiorespiratory and locomotor areas. J Appl Physiol 99: 2312–2322, 2005.[Abstract/Free Full Text]
  38. Osborn JW, Fink GD, Sved AF, Toney GM, Raizada MK. Circulating angiotensin II and dietary salt: converging signals for neurogenic hypertension. Curr Hypertens Rep 9: 228–235, 2007.[CrossRef][Web of Science][Medline]
  39. Pescatello LS, Franklin BA, Fagard R, Farquhar WB, Kelley GA, Ray CA, and American College of Sports Medicine. American college of sports medicine position stand. Exercise and hypertension. Med Sci Sports Exer 36: 533–553, 2004.[CrossRef][Web of Science][Medline]
  40. Roveda F, Middlekauff HR, Rondon MU, Reis SF, Souza M, Nastari L, Barretto AC, Krieger EM, Negrao CE. The effects of exercise training on sympathetic neural activation in advanced heart failure: a randomized controlled trial. J Am Coll Cardiol 42: 854–860, 2003.[Abstract/Free Full Text]
  41. Samson WK. Atrial natriuretic factor inhibits dehydration and hemorrhage-induced vasopressin release. Neuroendocrinology 40: 277–279, 1985.[CrossRef][Web of Science][Medline]
  42. Schiltz JC, Hoffman GE, Stricker EM, Sved AF. Decreases in arterial pressure activate oxytocin neurons in conscious rats. Am J Physiol Regul Integr Comp Physiol 273: R1474–R1483, 1997.[Abstract/Free Full Text]
  43. Scislo TJ, DiCarlo SE, Collins HL. Daily spontaneous running did not alter vagal afferent reactivity. Am J Physiol Heart Circ Physiol 265: H1564–H1570, 1993.[Abstract/Free Full Text]
  44. Share L. Control of vasopressin release: an old but continuing story. News Physiol Sci 11: 7–12, 1996.[Free Full Text]
  45. Share L. Role of vasopressin in cardiovascular regulation. Physiol Rev 68: 1248–1284, 1988.[Free Full Text]
  46. Stocker SD, Schiltz JC, Sved AF. Acute increases in arterial blood pressure do not reduced plasma vasopressin levels stimulated by angiotensin II or hyperosmolality in rats. Am J Physiol Regul Integr Comp Physiol 287: R127–R137, 2004.[Abstract/Free Full Text]
  47. Stocker SD, Smith CA, Kimbrough CM, Stricker EM, Sved AF. Elevated dietary salt suppresses renin secretion but not thirst evoked by arterial hypotension in rats. Am J Physiol Regul Integr Comp Physiol 284: R1521–R1528, 2003.[Abstract/Free Full Text]
  48. Stocker SD, Sved AF, Stricker EM. Role of renin-angiotensin system in hypotension-evoked thirst: studies with hydralazine. Am J Physiol Regul Integr Comp Physiol 279: R576–R585, 2000.[Abstract/Free Full Text]
  49. Stricker EM, Sved AF. Controls of vasopressin secretion and thirst: similarities and dissimilarities in signals. Physiol Behav 77: 731–736, 2002.[CrossRef][Medline]
  50. Thom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, Manolio T, Zheng ZJ, Flegal K, O'Donnell C, Kittner S, Lloyd-Jones D, Goff D, Hong Y, Adams R, Friday G, Furie K, Gorelick P, Kissela B, Marler J, Meigs J, Roger V, Sidney S, Sorlie P, Steinberger J, Wasserthiel-Smoller S, Wilson M, Wolf P, and American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2006 update: A report from the American Heart Association statistics committee and stroke statistics subcommittee. Circulation 113: e85–e151, 2006.[Free Full Text]
  51. Tidgren B, Hjemdahl P, Theodorsson E, Nussberger J. Renal neurohumoral and vascular responses to dynamic exercise in humans. J Appl Physiol 70: 2279–2286, 1991.[Abstract/Free Full Text]
  52. Veerasingham SJ, Raizada MK. Brain renin-angiotensin system dysfunction in hypertension: recent advances and perspectives. Br J Pharmacol 139: 191–202, 2003.[CrossRef][Web of Science][Medline]
  53. Wade CE, Claybaugh JR. Plasma renin activity, vasopressin concentration, and urinary excretory responses to exercise in men. J Appl Physiol 49: 930–936, 1980.[Abstract/Free Full Text]
  54. Zucker IH. Novel mechanisms of sympathetic regulation in chronic heart failure. Hypertension 48: 1005–1011, 2006.[Free Full Text]




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