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Am J Physiol Regul Integr Comp Physiol 278: R1634-R1642, 2000;
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Vol. 278, Issue 6, R1634-R1642, June 2000

Arterial baroreflex regulation of regional vascular conductance at rest and during exercise

Brenda Martínez-Nieves, Heidi L. Collins, and Stephen E. DiCarlo

Department of Physiology, School of Medicine, Wayne State University, Detroit, Michigan 48201


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

We tested the hypothesis that dynamic exercise resets the operating point and attenuates the spontaneous gain of the arterial baroreflex regulation of mesenteric and hindlimb vascular conductance in hypertensive rats. Eleven adult male spontaneously hypertensive rats were chronically instrumented with left carotid arterial catheters and Doppler ultrasonic flow probes around the superior mesenteric and left common iliac arteries. After the rats recovered, arterial baroreflex function was examined by recording reflex changes in conductance in response to spontaneous changes in mean arterial pressure before exercise and during steady-state treadmill running at 6 and 18 m/min. Dynamic exercise reduced the spontaneous baroreflex gain of mesenteric conductance (by 51 and 36%) and maximum mesenteric conductance (by 24 and 32%) at 6 and 18 m/min, respectively. In sharp contrast, dynamic exercise increased the spontaneous maximum iliac conductance (by 32 and 47%) without changing the spontaneous gain. Sinoaortic denervation eliminated the relationship between mean arterial pressure and conductance by reducing the mesenteric (92%) and iliac (68%) vascular conductance gain. These results demonstrate that dynamic exercise has differential effects on the regulation of mesenteric and iliac vascular conductance in hypertensive rats.

hypertension; spontaneous; resistance; operating point; blood pressure


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

FIFTY MILLION AMERICANS have hypertension or are taking antihypertensive medications (1). Furthermore, blood pressure regulatory mechanisms are less effective in controlling the circulation at rest in hypertensive subjects (7). The reduced blood pressure regulatory mechanisms may contribute, in part, to an increased level of arterial pressure (AP) and sympathetic nerve activity. It is unknown, however, whether dynamic exercise alters arterial baroreflex function in hypertensive subjects (6).

AP is a tightly regulated variable that is maintained within a narrow range by the arterial baroreflex (37). The arterial baroreflex functions as a short-term negative-feedback regulator of AP. Baroreflex regulation of AP is mediated by modulations in peripheral vascular conductance and cardiac output. However, most studies that have examined arterial baroreflex function at rest and during exercise have focused on the regulation of heart rate (HR) (6, 28) or AP (24, 30, 35). No studies have examined the influence of exercise on the arterial baroreflex regulation of regional conductance.

The arterial baroreflex regulation of HR at rest and during exercise has been investigated in normotensive humans (30, 35) and dogs (24) and hypertensive rats (6). The conclusion from these studies in normotensive humans and dogs (24, 30, 35) is that dynamic exercise is associated with a rapid upward resetting of the operating point without a change in gain of the arterial baroreflex. In sharp contrast, dynamic exercise results in an upward resetting of the operating point with a reduction in gain of the arterial baroreflex control of HR in hypertensive rats (6). Taken together, these studies suggest that the arterial baroreflex may be less effective in controlling circulation during exercise in hypertensive rats (28).

We tested the hypothesis that dynamic exercise resets the operating point and attenuates the spontaneous gain of the arterial baroreflex regulation of mesenteric and hindlimb vascular conductance in hypertensive rats. We studied hypertensive rats, because the resting level of sympathetic tone and the sympathetic response to exercise are exacerbated in hypertension (7-9). Furthermore, cardiovascular regulatory mechanisms are altered in hypertensive subjects (7). Finally, understanding baroreflex function in hypertensive subjects may lead to additional measures calculated to lower AP in hypertensive individuals. Arterial baroreflex function was determined by recording reflex changes in vascular conductance during spontaneous changes in AP. This spontaneous method eliminated many of the confounding influences of pharmacological changes in AP (6, 8, 14).


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Surgical Procedures

Intact condition. Eleven adult (16.1 ± 0.34 wk of age) male spontaneously hypertensive rats (283 ± 11 g) from our breeding colony were studied. After a 24-h fast, animals were anesthetized intramuscularly with a mixture of ketamine (40 mg/kg), xylazine (8 mg/kg), and chlorpromazine (4 mg/kg). Supplemental doses were administered if the rat regained the blink reflex or responded to the surgical procedures. With use of aseptic procedures, rats were instrumented with a polytetrafluoroethylene catheter inserted into the descending aorta via the left common carotid artery for measurements of AP. Subsequently, through a midline abdominal approach, an epoxy cuff-type pulsed Doppler ultrasonic flow probe was positioned around the left common iliac artery, and a silicone rubber cuff-type pulsed Doppler ultrasonic flow probe was positioned around the superior mesenteric artery. The catheter was flushed daily, filled with heparin (1,000 U/ml), and plugged with paraffin-filled obturators. Rats were carefully monitored for signs of infection and changes in body weight during the recovery period. All rats remained in a dedicated recovery area for 2 days after surgery. Subsequently, the rats were returned to their housing facilities. The rats were allowed to recover for >= 5 additional days before experimentation. During this time, the rats were familiarized with the treadmill and experimental procedures. At the time of the experimental protocols, all rats had recovered, were healthy, and were gaining weight.

Sinoaortic denervation condition. After completion of the experimental protocol in the intact condition, two of the intact rats and three additional rats underwent complete sinoaortic denervation (SAD). Rats were anesthetized as described above. An anterior cervical incision was made, and the carotid arteries were isolated at the region of the carotid sinus. All nerves and tissues were stripped from the sinus, the carotid artery, and all branches above and below the area of the sinus. The aortic depressor nerves were isolated bilaterally and sectioned. The animals were allowed 10 days to recover from the SAD procedure to ensure that they had adapted to the denervated state. Given the large increase in AP that occurs after acute denervation, it was important to wait until resting pressures had returned to predenervation levels to ensure that the animals were studied during steady-state conditions (2, 21, 25). The denervation procedure was verified as complete by elimination of a reflex HR response to changes in AP produced by infusions of phenylephrine (1.5 µg/kg) and nitroglycerin (0.15 mg/kg) (6, 8).

Experimental Measurements

AP was determined by connecting the arterial catheter to a Gould P23XL pressure transducer, which was coupled to a MacLab BRIDGE amplifier. The pulsed Doppler flow probes were connected to a multichannel ultrasonic flow dimension system with 20-MHz high-velocity modules constructed by the instrumentation development laboratories at Baylor College of Medicine. The Doppler flow dimensional system measures blood flow velocity in kilohertz of Doppler shift, which is directly proportional to absolute blood flow as determined with an electromagnetic system (16). AP and flow analog signals were digitized at 40 samples/s by a MacLab 8 analog-to-digital converter and laboratory computer (Macintosh Performa) for calculation of real-time HR, real-time mean AP (MAP), and real-time mean blood flow. Iliac and mesenteric vascular conductances were calculated by dividing mean blood flow (iliac and mesenteric) by MAP.

Experimental Protocol

Intact rats were habituated to the laboratory, treadmill, and investigators for >= 5 days before the experimental protocol began. Once it was determined that the animals would run at each workload without aversive stimuli, each rat underwent one graded exercise test, as previously described (12). Briefly, on the day of the experiment, the intact rats were placed on the treadmill to obtain baseline hemodynamic data and spontaneous baroreflex responses. Control values for AP and HR were recorded for a 2-h baseline period. At the end of the 2-h baseline period, the rats ran on the treadmill at 6 m/min and 10% grade for a total of 3 min, while the data were continuously recorded. After hemodynamic variables reached a steady state (~2 min), a minimum of three spontaneous baroreflex responses was recorded. Subsequently, the speed of the treadmill was gradually increased to 18 m/min. Animals ran at 18 m/min for a total of 3 min. AP and HR reached a steady state after ~2 min. At this time, a minimum of three spontaneous baroreflex responses was recorded. We examined data during the last minute of each workload for a minimum of three spontaneous changes in AP and reflex responses in conductance. Data obtained during these periods were included for analysis. A minimum of three spontaneous baroreflex function relationships was generated for each animal at each workload. The parameters from the three function relationships at each workload were averaged to obtain one relationship for each animal at each workload.

The SAD group was studied only before exercise by utilizing procedures identical to those used for the intact rats. The SAD rats were habituated to the laboratory and investigators for >= 5 days before the experimental protocol began. On the day of the experiment, the SAD rats were placed on the treadmill to obtain baseline hemodynamic data and spontaneous baroreflex responses. Control values for AP and HR were recorded for a 2-h baseline period.

Evaluation of Spontaneous Arterial Baroreflex Regulation of Conductance

Absolute values for mesenteric and iliac artery conductance were used to assess the capability of the arterial baroreflex to regulate conductance during spontaneous changes in MAP. Raw data points were collected on a beat-to-beat basis. For the analysis of the relationship between MAP and the spontaneous changes in conductance, the computer recorded MAP for each calculated conductance value. The threshold or minimum change in MAP required to generate the pressure-conductance relationships was 7.00 ± 0.66 mmHg. These pressure values were then plotted against the calculated conductance after a 3.56 ± 0.18 and a 2.78 ± 0.10 s phase shift from MAP to the change in mesenteric and iliac conductance, respectively. This time shift (time lag) was calculated by determining the time between the start of the spontaneous change in AP and the start of the reflex change in conductance. No threshold or minimal change in conductance was required if the change in MAP exceeded the threshold. Because spontaneous changes in pressure generated a linear relationship for the arterial baroreflex regulation of conductance, the data from each animal were fit by a linear regression, with conductance being regressed on MAP. The coefficient of determination (r2) was used to quantify the quality of the relationship between AP and vascular conductance (29). The slope of the regression line was used as an indicator of the overall spontaneous gain or spontaneous arterial baroreflex sensitivity for each animal under each experimental condition. By use of the regression equation, the following arterial baroreflex function parameters were calculated: the spontaneous range of conductance (C1), the spontaneous minimum conductance response (C2), the spontaneous maximum conductance response (C3, the sum of C1 and C2), the midpoint of the spontaneous conductance range (C4), and the midpoint of the spontaneous pressure range (P1).

Data Analysis

Values are means ± SE. Unpaired t-tests were used to determine the differences in the r2 values between the intact and the SAD condition. One-way ANOVAs were used to determine the differences in baroreflex function parameters at rest and during exercise (Table 1). One-way ANOVAs were used to compare the differences between hemodynamic variables at rest and at each workload (6 and 18 m/min; see Fig. 3). Differences observed at the different workloads and baroreflex function parameters were further evaluated using Fisher's least significant difference test. Two separate two-way ANOVAs were used to compare the relationships between MAP and conductance (mesenteric and iliac) at rest and during exercise (see Fig. 4). Significance was set at P <=  0.05. All conductance values were multiplied by 100. 

                              
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  		Table 1.   Baroreflex function parameters and coefficient of determination for arterial baroreflex control of mesenteric and iliac artery conductance in intact rats


    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Figure 1 presents actual data points that illustrate the relationship between spontaneous changes in MAP and reflex responses of mesenteric and iliac conductance for one rat before and during dynamic exercise at 6 and 18 m/min. As the exercise intensity increased, there was a progressive shift of the operating point to a higher pressure and a corresponding change in vascular conductance. Figure 2 is an analog recording showing AP, HR, and mesenteric and iliac blood flow at rest and during exercise (6 and 18 m/min) for one rat. Graded exercise significantly increased HR and iliac blood flow. In contrast, MAP and mesenteric blood flow did not significantly change from preexercise.


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  		Fig. 1.   Actual data points illustrating relationship between spontaneous changes in mean arterial pressure (MAP) and reflex changes in mesenteric (A) and iliac (B) conductance before exercise and during dynamic exercise at 6 and 18 m/min in 1 male spontaneously hypertensive rat. Data points for each animal were fit by a linear regression, with conductance regressed on MAP. Slope of regression line was used as an index of overall spontaneous arterial baroreflex sensitivity or spontaneous gain for each animal under each condition. Dynamic exercise attenuated spontaneous gain of arterial baroreflex regulation of mesenteric conductance in intact spontaneously hypertensive rats.



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  		Fig. 2.   Analog recording showing arterial pressure, heart rate, and mesenteric and iliac blood flow (MBF and IBF, respectively) at rest and during 2 stages of graded exercise in intact rats. Dynamic exercise increased heart rate and iliac blood flow; arterial pressure and mesenteric blood flow did not change significantly from rest.

Figure 3 presents mean data for MAP, HR, mesenteric and iliac blood flow, and mesenteric and iliac vascular conductance at rest and during exercise at 6 and 18 m/min. Before exercise, MAP, HR, mesenteric and iliac blood flow, and mesenteric and iliac vascular conductance averaged 176 ± 4 mmHg, 357 ± 11 beats/min, 5.36 ± 0.55 kHz, 4.33 ± 0.44 kHz, 3.08 ± 0.34 kHz/mmHg, and 2.48 ± 0.26 kHz/mmHg, respectively. As anticipated, HR (437 ± 19 beats/min) significantly increased during treadmill running at 6 m/min, whereas mesenteric blood flow (5.11 ± 0.61 kHz), iliac blood flow (5.73 ± 0.64 kHz), MAP (185 ± 6 mmHg), mesenteric conductance (2.80 ± 0.35 kHz/mmHg), and iliac conductance (3.14 ± 0.38 kHz/mmHg) did not change significantly at 6 m/min. As the workload increased, there was a significant increase in HR (494 ± 20 beats/min), iliac blood flow (7.15 ± 0.87 kHz), and iliac conductance (3.88 ± 0.48 kHz/mmHg) during exercise at 18 m/min; however, MAP (186 ± 5.0 mmHg), mesenteric blood flow (4.06 ± 0.54 kHz), and mesenteric conductance (2.23 ± 0.33 kHz/mmHg) did not change significantly from rest.


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  		Fig. 3.   MAP, heart rate, mesenteric and iliac blood flow, and mesenteric and iliac conductance at rest and during exercise at 6 and 18 m/min. Dynamic exercise increased heart rate, iliac blood flow, and iliac conductance; MAP, mesenteric blood flow, and mesenteric conductance did not change significantly from exercise. Values are means ± SE. * P <=  0.05 vs. rest; § P <=  0.05 vs. 6 m/min in intact rats.

Figure 4 presents the group means for the spontaneous arterial baroreflex regulation of mesenteric and iliac conductance before and during dynamic exercise in intact animals. These data demonstrate that dynamic exercise significantly reduced the gain of the spontaneous arterial baroreflex regulation of the mesenteric conductance. The spontaneous arterial baroreflex regulation of the mesenteric conductance was operating at a higher pressure and with a reduced conductance and gain. In contrast, the spontaneous gain of the arterial baroreflex regulation of iliac conductance was not altered by exercise. However, the spontaneous arterial baroreflex regulation of iliac conductance was operating at a higher pressure and conductance. Specifically, there was a significant workload effect, indicating that exercise significantly altered the arterial baroreflex regulation of mesenteric and iliac conductance.


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  		Fig. 4.   Spontaneous arterial baroreflex regulation of conductance in intact rats. Mean minimum and maximum mesenteric (A) and iliac (B) conductance are shown with associated MAP before and during dynamic exercise at 6 and 18 m/min. Each grade of exercise shifted arterial baroreflex control of mesenteric conductance downward and to right, and this shift was accompanied by a reduction in spontaneous range and gain. There was a significant workload effect, indicating that exercise significantly altered arterial baroreflex regulation of mesenteric and iliac conductance. * P <=  0.05.

Table 1 presents the spontaneous arterial baroreflex function parameters and the r2 value for the control of mesenteric and iliac conductance before and during dynamic exercise. Dynamic exercise significantly reduced the spontaneous minimum mesenteric conductance, midpoint mesenteric conductance, and spontaneous gain. Dynamic exercise also significantly increased the MAP midpoint. In contrast, dynamic exercise did not significantly alter baroreflex regulation of iliac conductance.

The SAD procedure was verified as complete by a significant reduction of the reflex HR response to changes in AP produced by infusions of phenylephrine (1.5 µg/kg) and nitroglycerin (0.15 mg/kg). Before SAD, phenylephrine produced a 22 ± 3 mmHg increase in MAP with a decrease in HR of 54 ± 5 beats/min. Nitroglycerin produced a 26 ± 2 mmHg decrease in MAP with an increase in HR of 42 ± 12 beats/min. After SAD, phenylephrine produced a 34 ± 0 mmHg increase in MAP with a decrease in HR of 1 ± 3 beats/min. Nitroglycerin produced a 28 ± 4 mmHg decrease in MAP with a paradoxical decrease in HR of 3 ± 7 beats/min.

SAD reduced the spontaneous gain of the arterial baroreflex regulation of mesenteric (92%) and iliac (68%) conductance (Table 2). Furthermore, SAD significantly attenuated the relationship between MAP and mesenteric and iliac conductance by reducing r2 by 80 and 26%, respectively (Table 2). Specifically, in the intact condition the r2 values for the relationship between MAP and mesenteric and iliac conductance before exercise were 0.71 ± 0.02 and 0.75 ± 0.02, respectively. However, in the SAD condition, the r2 values for the relationship between MAP and mesenteric and iliac conductance at rest were 0.14 ± 0.04 and 0.55 ± 0.03, respectively. These results are verified in Fig. 5. Figure 5 presents the group means for the spontaneous arterial baroreflex regulation of mesenteric and iliac conductance at rest. These data document that SAD significantly reduced the relationship between AP and vascular conductance.

                              
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  		Table 2.   Baroreflex function parameters and coefficient of determination for arterial baroreflex control of mesenteric and iliac artery conductance at rest in SAD rats



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  		Fig. 5.   Spontaneous arterial baroreflex regulation of conductance in sinoaortic denervated rats. Mean minimum and maximum mesenteric and iliac conductance are shown with associated MAP before exercise. Sinoaortic denervation significantly reduced spontaneous gain and coefficient of determination of arterial baroreflex control of mesenteric and iliac conductance.


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

It is well documented that dynamic exercise is associated with marked vasoconstriction and diversion of blood flow from nonexercising tissues, especially the splanchnic, renal, and cutaneous vascular beds in normotensive subjects (15). The exercise-induced vasoconstriction in nonactive vascular beds may be mediated via the arterial baroreflex (15). Importantly, arterial baroreflex-mediated vasoconstriction in the active skeletal muscle is also important for the regulation of AP (15, 27, 41). Vascular conductance of active skeletal muscle may exceed the pumping capacity of the heart, resulting in a reduction in AP without sympathetic restraint on vascular conductance (39, 41). Therefore, understanding the arterial baroreflex regulation of vascular conductance in active and nonactive vascular beds during exercise will contribute to our understanding of cardiovascular and exercise physiology. Results from this study demonstrate that dynamic exercise shifts the operating point of the arterial baroreflex regulation of vascular conductance to a higher pressure. Importantly, the spontaneous gain of the arterial baroreflex control of mesenteric conductance was significantly reduced. However, dynamic exercise did not alter the spontaneous gain of the arterial baroreflex regulation of iliac conductance. These results demonstrate that dynamic exercise has differential effects on the regulation of mesenteric and iliac conductance in hypertensive rats. The differential arterial baroreflex function may facilitate the control of AP during the stress of exercise.

The arterial baroreflex regulates AP via reflex changes in cardiac output and vascular conductance. This is the first study that examined the influence of dynamic exercise on the arterial baroreflex regulation of vascular conductance in nonactive and active vascular beds. Previous studies have determined the influence of dynamic exercise on the arterial baroreflex regulation of HR (6, 24, 30, 35) and AP (24, 30, 35). Although these previous studies have significantly contributed to our understanding of arterial baroreflex function during exercise, these studies have also raised important questions. Specifically, an analysis of only HR to assess baroreflex function is limited, since alterations in HR only examine one efferent limb of the reflex (37). The other limb is vascular conductance, which in some circumstances can comprise the major or only correction for the change in blood pressure (22, 37). Furthermore, changes in HR may not accurately reflect changes in cardiac output.

The studies that examined the arterial baroreflex regulation of AP during exercise (24, 30, 35) have also raised significant questions, because these studies were conducted in humans and dogs. Studies in dogs present specific concerns. Blood flow is diverted away from nonactive tissues during dynamic exercise in humans (36), baboons (18, 43), sheep (3), ponies (31), rabbits (11, 15, 23), and rats (32). However, normal dogs (because of the large heart weight-to-body weight ratio and large cardiac reserve) do not redistribute blood away from nonactive tissues during exercise (17, 38, 44). These data suggest that the arterial baroreflex in the dog may not play the same role that it does during exercise in other species with low cardiac reserve.

In humans, carotid sinus baroreflex regulation of AP during exercise has been examined by applying positive and negative pressures at the neck and observing changes in AP. One concern with this approach is that intact aortic baroreceptors oppose the reflex change in systemic AP (37).

Finally, all previous studies, with the exception of one (6), have examined the influence of dynamic exercise on arterial baroreflex function in normotensive subjects. However, 50,000,000 Americans have hypertension or are taking antihypertensive medication. Hypertension is the single most important contributing factor to coronary heart disease and stroke (1). Cardiovascular diseases, including coronary heart disease, ventricular arrhythmias, and stroke, as well as renal disease and all-cause mortality, increase progressively with higher levels of AP. In addition, arterial and cardiopulmonary baroreflexes are less effective in controlling the circulation in hypertensive subjects, and cardiovascular regulatory mechanisms are different from those in normotensive subjects (7). Therefore, it is important to understand the integrative mechanisms that regulate AP in hypertensive populations so that appropriate interventions can be developed.

The results from the present study address some of these questions. First, this is the first study to examine this question in rats, an animal with a low heart weight-to-body weight ratio and limited cardiac reserve. With the limited cardiac reserve, the arterial baroreflex plays an important role in regulating vascular conductance. Furthermore, because a large number of investigators study smaller species (rats, rabbits, and increasingly mice) to understand autonomic control mechanics, it was important to examine these questions in the rat. Second, the studies were conducted in the hypertensive model. The results in hypertensive subjects will extend our understanding of cardiovascular control in pathophysiological conditions and may result in interventions designed to lower blood pressure. Furthermore, the resting level of sympathetic tone and the sympathetic response to exercise are exaggerated in hypertensive vs. normotensive rats (7), and the baseline level of sympathetic tone influences arterial baroreflex function (28). Finally, arterial baroreflex control of vascular conductance in nonactive and active tissues was examined. Autonomic regulation of cardiac output and vascular conductance is central for the animal to exercise and consume oxygen (40). Thus understanding arterial baroreflex control of vascular conductance during exercise merits further investigation.

Influence of SAD on the Arterial Baroreflex Regulation of Conductance

Spontaneous arterial baroreflex function was evaluated in SAD rats to determine whether the arterial baroreflex was responsible for the reflex responses in conductance after spontaneous changes in MAP. SAD significantly attenuated the relationship between MAP and conductance by reducing the spontaneous gain and the r2 value (Table 2, Fig. 5). Specifically, SAD virtually eliminated the relationship between conductance and pressure for the mesenteric bed (0.71 ± 0.02 to 0.14 ± 0.04). However, the reduction in the r2 value for the iliac bed (0.75 ± 0.02 to 0.55 ± 0.03) was not as impressive. Together, these results document that spontaneous changes in MAP elicited a reflex response in conductance that required a functional arterial baroreflex. Similarly, previous studies in our laboratory have demonstrated that SAD significantly attenuates the relationship between AP and HR by reducing the spontaneous gain and the correlation coefficient (6, 8).

Mechanisms for Arterial Baroreflex Resetting

The mechanism responsible for the exercise-induced shift of the operating point of the arterial baroreflex to a higher pressure and the reduction in the spontaneous gain of the arterial baroreflex regulation of mesenteric conductance in hypertensive animals is unknown. However, peripheral and central mechanisms may contribute to the altered arterial baroreflex responses. For example, the exercise-induced increase in AP may desensitize baroreceptor afferents, resulting in reduced afferent input to the central nervous system. In contrast, the exercise-induced increase in HR and cardiac contractility may activate cardiopulmonary receptors (4, 10). The cardiopulmonary baroreflex exerts an inhibitory interaction with the arterial baroreflex. Similarly, activation of muscle afferents, which are known to have an inhibitory interaction with the arterial baroreflex, may also contribute to the alterations in baroreflex function (33, 34). Alterations during exercise could also occur at the efferent side of the reflex. Specifically, we (13, 19, 20) and others (5, 42) have documented that exercise reduces alpha -adrenergic receptor-mediated vasoconstrictor responses. These data suggest that, after exercise, baroreflex-mediated changes in sympathetic nerve activity may be less effective in causing vasoconstriction. Although these data may explain the reduced arterial baroreflex responses in the mesenteric vasculature, it cannot explain the response in the iliac vasculature. The differential responses in the active and nonactive vascular beds merit further investigation. Finally, the observed results may also be due to central mechanisms, since we cannot rule out changes within the brain stem/bulbospinal pathways.

Functional Significance

It is important that the gain of the arterial baroreflex control of iliac vascular conductance is not altered during exercise. In order for arterial baroreflex-mediated changes in sympathetic activity to have a significant effect on AP, sympathetic activity must be directed to the vascular beds that make the greatest contribution to total vascular conductance. During exercise, mesenteric vascular conductance contributes very little to total vascular conductance (26, 27). In this situation, regulating mesenteric vascular conductance would have little impact on AP. In sharp contrast, iliac vascular conductance makes the greatest contribution to total vascular conductance during exercise. In this situation, regulation of sympathetic activity to this bed has a profound influence on AP (26, 27, 41). Taken together, these data suggest that AP regulation would not be altered during exercise in hypertensive rats, since the arterial baroreflex regulation of iliac vascular conductance is not altered.

The onset of dynamic exercise causes an immediate increase in the metabolic rate of the active muscle and an increase in total vascular conductance. Importantly, the increase in cardiac output is delayed so that there is a mismatch between cardiac output and vascular conductance. This mismatch is accommodated by vasoconstriction in and diversion of blood flow from the splanchnic organs, kidneys, skin, and fat (15). Thus mesenteric vasoconstriction, which has been demonstrated to be mediated by the arterial baroreflex (15), is important for the redistribution of blood flow during exercise.

Assessment of the Spontaneous Method

We (6, 8) and others (14) recently discussed the advantages and disadvantages of using perturbational and nonperturbational (spontaneous) methods to assess arterial baroreflex function. The perturbational methods for the evaluation of arterial baroreflex function have several inherent limitations, such as the indirect influence of pharmacological agents and the need for extensive surgical procedures to alter AP. These limitations have motivated investigators to consider nonperturbational methods for the evaluation of arterial baroreflex function. However, there is no perfect methodology to examine arterial baroreflex function.

Similar to the perturbational methods for determining arterial baroreflex function, the spontaneous method also has limitations. It is possible that spontaneous changes in central venous pressure and respiratory gating of baroreflex sensitivity may have a greater impact on nonperturbational baroreflex determinations than large pharmacologically induced changes in AP. Moreover, in contrast to perturbational methods that allow the assessment of a large range of pressures (i.e., from threshold to saturation) for the assessment of arterial baroreflex function, the spontaneous method assesses a limited range. Consequently, it is inappropriate to compare responses obtained by the spontaneous arterial method with those obtained by the perturbational methods, since these parameters were attained under different physiological conditions.

Although the spontaneous method assesses the arterial baroreflex over a limited range of AP, this is the physiological range of pressure. Under physiological conditions, the arterial baroreflex functions on a beat-to-beat basis to regulate AP within a narrow range. Under these physiological conditions, the relationship between MAP and HR (6, 8) and vascular conductance is linear. Furthermore, the perturbational method, by causing large changes in AP, may introduce nonphysiological artifacts.

In summary, results from this study demonstrated that dynamic exercise shifted the operating point of the arterial baroreflex to a higher pressure and reduced the spontaneous gain of the arterial baroreflex control of mesenteric conductance in male spontaneously hypertensive rats. In sharp contrast, dynamic exercise did not alter the arterial baroreflex regulation of iliac conductance. Thus dynamic exercise has differential effects on the arterial baroreflex regulation of mesenteric and iliac vascular conductance in hypertensive rats. Importantly, the fact that the gain of the arterial baroreflex regulation of iliac conductance was not different between rest and exercise suggests that the regulation of AP would not be altered by exercise.

Perspectives

The investigation of the arterial baroreflex regulation of vascular conductance in nonactive and active vascular beds during exercise is a key factor in understanding the integrative reflex control of the circulation, since more can be learned about how a system operates when it is forced to perform than when it is idle (37). Furthermore, understanding arterial baroreflex function at rest and during exercise in a hypertensive model may result in interventions designed to lower AP and sympathetic nerve activity. The spontaneous approach, used in this study to assess arterial baroreflex function, provides a physiological method to examine the influence of dynamic exercise on the arterial baroreflex regulation of vascular conductance. In addition, an examination of vascular conductance complements recent work examining the arterial baroreflex regulation of HR (6). Together, these studies provide data on the integrative mechanisms that regulate AP in hypertensive populations.


    ACKNOWLEDGEMENTS

This study was supported by the National Heart, Lung, and Blood Institute Grant HL-58414 and the Minority Post-Doctoral Training Supplement.


    FOOTNOTES

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. §1734 solely to indicate this fact.

Address for reprint requests and other correspondence: S. E. DiCarlo, Dept. of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201 (E-mail: sdicarlo{at}med.wayne.edu).

Received 4 July 1999; accepted in final form 21 December 1999.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

1.   Anonymous Fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med 153: 154-183, 1993[Abstract/Free Full Text].

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Am J Physiol Regul Integr Comp Physiol 278(6):R1634-R1642
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