Comprehensive Physiology Wiley Online Library

Integration of Cardiovascular Control Systems in Dynamic Exercise

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Abstract

The sections in this article are:

1 I. Intrinsic Properties of the Cardiovascular System: How They Permit the Rise in Cardiac Output
2 The Heart
2.1 Intrinsic Properties of the Heart
2.2 Pericardial Constraints
3 The Vascular System
3.1 Distribution of Resistance, Conductance, and Compliance
3.2 Dependency of CVP on Cardiac Output
3.3 Mechanical Effects on the Circulation—Auxiliary Pumps
3.4 Does Exercise Reduce Systemic Vascular Compliance?
3.5 Neural Control of the Vascular System during Exercise: How Important?
3.6 Balance between Mechanical and Neural Effects on Blood Flow and Blood Volume Distribution
4 II. Reflex Control of the Cardiovascular System During Dynamic Exercise: What Variables are Sensed and then Regulated by the Autonomic Nervous System During Dynamic Exercise?
4.1 Central Command
4.2 Reflexes from Active Muscles
5 Isometric Contractions: Testing Hypotheses
5.1 Isometric Contractions vs. Dynamic Exercise
5.2 Open‐Loop vs. Closed‐Loop Conditions
5.3 Does the Pressor Response to Voluntary Isometric Contraction have Chemoreflex or Mechanoreflex Origin?
6 Functional Importance of Muscle Chemoreflexes During Dynamic Exercise
6.1 Basic Concepts and Theory
6.2 Changes in MSNA as Evidence for Chemoreflex Activity in Dynamic Exercise
6.3 Does the Muscle Chemoreflex Initiate Increased SNA during Dynamic Exercise with Unimpaired Flow?
6.4 Does Activation of the Muscle Chemoreflex Correct Blood Flow Errors, and if so, How?
7 Baroreflex Regulation of Arterial Pressure (SAP) and Vascular Conductance in Dynamic Exercise
7.1 Does the Arterial Baroreflex Control SAP During Exercise?
7.2 Characterization and Analysis of Arterial Baroreflex Function
7.3 Baroreflex Sensitivity in Dynamic Exercise
7.4 Importance of Arterial Baroreflexes at the Onset of Exercise
7.5 Evidence Indicating “Resetting” of the Arterial Baroreflex
7.6 Central Command and Resetting of the Arterial Baroreflex—An Hypothesis
8 Role of Cardiopulmonary Baroreceptors in Dynamic Exercise
8.1 The Cardiopulmonary, or Low‐Pressure, Baroreflex
8.2 Interaction between the Cardiopulmonary and Arterial Baroreflexes at Rest
8.3 Role of Cardiopulmonary Baroreflex during Dynamic Exercise
8.4 Interaction between Cardiopulmonary Baroreflex and Muscle Chemoreflex
8.5 Interaction between Cardiopulmonary and Arterial Baroreflexes in Exercise
8.6 Importance of Cardiopulmonary Baroreflexes during Dynamic Exercise
9 Control of the Circulation During Exercise and Heat Stress: Competing Reflexes
9.1 Cardiovascular Demands of Heat Stress
9.2 Overall Neural Control of the Cutaneous Circulation
9.3 Reflex Control of the Cutaneous Circulation during Exercise
9.4 Baroreflex v. Thermoregulatory Reflex Control of the Cutaneous Circulation during Exercise
10 How Does Physical Conditioning Alter Cardiovascular Function?
10.1 Range of Adjustment in Overall Cardiovascular Function
10.2 What Cardiovascular Adjustments Explain the Rise in V.O2max?
10.3 How does Maximal SV Increase with Physical Conditioning?
10.4 Does Physical Conditioning Change Autonomic Control of the Circulation?
11 Synthesis
11.1 What is the Autonomic Nervous System Controlling during Exercise?
11.2 What Errors Are Sensed and then Corrected by the Autonomic Nervous System during Exercise?
Figure 1. Figure 1.

Right atrial and pulmonary wedge pressures during seated rest and five levels of upright dynamic leg exercise (cycling). Note relationship between wedge and right atrial pressure and abrupt rise in both pressures at peak exercise.

Adapted from Reeves et al. with permission
Figure 2. Figure 2.

Abrupt rise in mean right atrial (R.A.) pressure at onset of upright treadmill exercise. Sudden return of blood to the heart by skeletal muscle pump transiently exceeds left ventricular output [mean brachial arterial pressure (B.A.) also shown].

Adapted from Robinson et al.
Figure 3. Figure 3.

A, Relationship between left atrial pressure (LA) and left ventricular (LV) segment length at end‐diastole in one pig at 1 day (1d) and 8 days (8d) after thoracotomy without (solid circles) and with (open circles) pericardiectomy. B, Average stroke volumes before (open bars, N) and after (hatched bars, P) pericardiectomy. Data averaged from five pigs during three levels of treadmill exercise shown as percentage grade at 80–91 m/min.

Adapted from Hammond et al. with permission
Figure 4. Figure 4.

Effects of changing cardiac output by ventricular pacing on right atrial pressure in supine human subjects during rest (open circles) and exercise (cycling) (solid circles) [From Bevegard et al. .] Results were similar to those of Sheriff et al. on resting and exercising dogs (see Chapter ). Increments in cardiac output at rest caused by raising skin blood flow [Rest + Heat (solid triangles) from Rowell ], or further increments in cardiac output during exercise also caused by raising skin blood flow [Exercise + Heat (solid squares) from Rowell et al. ] also reduced right atrial pressure in proportion to the rise in cardiac output. Slopes during heating with and without exercise were obtained from different subjects in separate studies.

Figure 5. Figure 5.

Schematic illustration of the pressure profile across the vascular system. Up to the capillaries pressure oscillations characterize only the changing magnitudes of pulse pressure and not cardiac frequency. The circuit is broken in the muscle by the muscle pump, and pressure oscillations show external effects of muscle pumping and then respiratory pumping—four pumps in series. Blood flow from the left ventricle to the muscle is determined by the pressure difference between the heart and some unknown point in the muscle, whereas blood flow from active muscle to the right ventricle is determined by the force provided by the muscle pump.

Reproduced from Rowell with permission
Figure 6. Figure 6.

Summary of human sympathetic responses to mild to maximal dynamic exercise. Response pattern was unaffected by ambient temperature, active muscle mass, or physical conditioning . Sympathetic nervous activity begins to rise when vagal withdrawal is nearly complete and heart rate approaches 100 bpm. The indices of increased SNA are splanchnic and renal vasoconstriction (decline in RBF and SBF), increased plasma norepinephrine (NE) concentration, and plasma renin activity (PRA). Cutaneous, coronary, and skeletal muscle arterioles also constrict, suggesting diffuse sympathetic outflow. Also, MSNA (burst frequency) rises with HR up to near maximal values (see Fig. ). Lactic acid (HLa) does not rise until HR reaches 130–140 bpm (50%–60% of VO2max) or much higher in athletes.

Adapted from Rowell and O'Leary
Figure 7. Figure 7.

Renal neurohormonal responses to graded dynamic exercise (supine posture) in eight normal young humans. Exercise levels were 69, 132, and 188 W. Arteriovenous differences across the kidney (left column) and renal overflows (right column) of norepinephrine, immunoreactive neuropeptide Y, renin, and dopamine are related to the average heart rates during exercise. The renal arteriovenous differences for angiotensin (lower left) and also for epinephrine (not shown) were positive, showing net renal uptake of these hormones. The average values for renal blood flow at the three heart rates fall on the regression line for RBF vs. HR shown in Figure . Note the similar response pattern among all indices of RSNA.

Redrawn from Tidgren et al. and reproduced from Rowell with permission
Figure 8. Figure 8.

During 20 min of moderately heavy (65% of maximal workrate) leg exercise (upright cycling), HR, plasma NE concentration, and NE spillover rate rose continuously, whereas NE clearance was reduced slightly and significantly only at 30 min . *P < 0.05 compared with resting and P < 0.05 compared with 5 min exercise value. The increments in plasma NE and NE spillover are probably associated with the decline in mean arterial pressure (MAP).

From Leuenberger et al. with permission
Figure 9. Figure 9.

Muscle sympathetic nerve activity (MSNA) in resting legs increases in proportion to intensity of dynamic arm exercise (cycling). Data are unillustrated from a subject‐coauthor studied by Victor et al. . This subject could exercise at 80 W before body motion made microneuro‐graphic measurements of MSNA from a peroneal nerve impossible. Two important features are (1) there was a threshold for the rise in MSNA at 40 W (for all subjects), and (2) the delay in the rise in MSNA decreased with increasing work intensity and may have been almost absent at 80 W.

From original data kindly provided by D. R. Seals and reproduced from Rowell with permission
Figure 10. Figure 10.

A, Relationship between MSNA (expressed as Δburst frequency from the median nerve) and percentage of during dynamic leg exercise (cycling) at approximately 20%, 40%, 60%, and 75% . Disagreement with interpretation of Saito et al. is revealed by two sets of regression lines: dashed line by Saito et al., solid line by us. The ΔMSNA was calculated from “baseline” values (Δ = 0) that had been elevated by orthostatic stress (seated upright rest). Mild exercise and muscle pump restored CVP and aortic pulse pressure, thus lowering MSNA to supine resting values. MSNA appeared not to rise until work required 40% (rising solid line) (horizontal solid line illustrates our assumption that the slope of MSNA response is zero below 40% ). B, Relationship between MSNA and HR based on our interpretation (solid lines) is consistent with other findings and with Figure [see also Victor et al. ]. Dashed line of Saito et al. shows no HR threshold for MSNA.

Adapted from Saito et al.
Figure 11. Figure 11.

Differential responses to lumbar sympathetic nerve stimulation during rest and maximal contractions of rat gastrocnemius‐plantaris and soleus muscles. During contractions of the gastrocnemius‐plantaris, sympathetic stimulation had no effect on femoral vascular conductance so that blood flow rose passively with a sympathetically mediated rise in SAP. Vasoconstriction was prevented by the dominance of metabolite‐sensitive α2‐adrenoceptors in this glycolytic muscle. Conversely, the dominance of metabolite‐insensitive α1‐adrenoceptors in oxidative soleus muscle is revealed in the maintained vasoconstriction and fall in femoral vascular conductance during sympathetic stimulation combined with muscle contraction. A potential problem in interpreting these results is noted in the text.

From Thomas et al. with permission
Figure 12. Figure 12.

Evidence showing sympathetic modulation of both muscle blood flow and in rhythmically contracting human forearm muscles. A, Forearm blood flow (FBF) before (open circles) and after (solid circles) stellate ganglion block, measured as changes from resting flow before and after nerve block. B, Forearm (from calculated arterial and measured deep venous O2 contents and FBF) also rose with higher forearm blood flow, suggesting that had also been depressed by tonic SNA before blockade. *P < 0.05.

Adapted from Joyner et al. with permission
Figure 13. Figure 13.

Influence of autonomic blockade (hexamethonium + atropine) on the hemodynamic responses to mild treadmill exercise in dogs. Despite the maintenance of normal cardiac output by ventricular pacing (after ∼30 s), arterial pressure fell to 55 mm Hg during mild treadmill exercise after autonomic blockade (solid circles). Total vascular conductance (and hindlimb vascular conductance, not shown) continued to rise 60 s after blockade. Conversely, conductance fell after reaching a peak near 10 s when sympathetic nerves were not blocked (open circles).

From Sheriff et al. with permission
Figure 14. Figure 14.

A, The volume of blood available to fill the heart depends on the distribution of blood flow between compliant (C1) and noncompliant (C2) circuits. In exercise, active muscle [noncompliant circuit (C2)] becomes another pump actively returning blood to the heart. Cardiac filling pressures are determined by effectiveness of muscle pumping and sympathetic control of other circuits (e.g., C1); that is, in effect the ratios of blood flows through C1 and C2. B, The relationship between venous volume and blood flow in a compliant (C1) region (e.g., splanchnic or skin) and a noncompliant region (C2) (e.g., muscle). Line C2 shows no increase in venous volume with increased perfusion of resting muscle. Dashed line with arrow shows that muscle pump (MP) reduces venous volume.

Adapted from Rowell with permission
Figure 15. Figure 15.

A scheme for coordination of feedforward and feedback control of the cardiovascular system during exercise. Motor system signals used to initiate locomotion initiate feedforward actions (central command) on the cardiovascular system. Coordination with feedback control (the arterial baroreflex) is accomplished by sending the feedforward command to the feedback controller, which resets the operating point for arterial pressure regulation during exercise.

Adapted from Houk and reproduced from Rowell with permission
Figure 16. Figure 16.

Schematic illustration to demonstrate relative responses to central command (CC), muscle chemoreflex (CR), and muscle mechanoreflex (MR) during a powerful isometric contraction. A, Normal rise in arterial pressure is achieved initially by CC and some MR component. After about 1 min, CR may contribute to rise in pressure. Time course of CR is derived from ΔMSNA (arbitrary units) in bottom panel. Vascular occlusion (Occl.) of active limb at end of contraction prevents normal recovery (NR) of pressure. This is the test for a muscle chemoreflex. Pressure drops approximately 50% when CC ceases and is kept elevated by CR as long as ischemia persists. B, Heart rate is raised by CC (some MR?) via vagal withdrawal. C, MSNA is presumably increased by CR and remains elevated during post‐exercise ischemia (shaded region reveals variations in response).

Adapted from Rowell and O'Leary
Figure 17. Figure 17.

Schematic illustration of responses to the muscle chemoreflex during mild and moderate dynamic exercise. A, Mild exercise. Graded partial occlusions of the terminal aorta of an exercising dog generate graded decrements in terminal aortic flow (TAQ) and femoral arterial pressure, but arterial pressure (SAP) will not rise, and TAQ will not be partially restored until the chemoreflex becomes active—which happens at the second through fourth occlusions. The rise in SAP causes an ∼50% recovery of TAQ and femoral arterial pressure. B and C, Stimulus–response curves for the chemoreflex show that the reflex has a threshold (T). “Prevailing” TAQ (F, in panel B) and femoral arterial pressure (P, in panel C) represent their normal operating levels in exercise—which are on the flat (low‐gain) parts of the curves. Therefore, the chemoreflex is not tonically active and SAP does not rise until TAQ and/or femoral arterial pressure fall below some critical level (at T). D, Moderate dynamic exercise. Shows characteristic responses of a tonically active muscle chemoreflex. E and F show prevailing TAQ and P are on (or just at) the steep (high‐gain) portion of the stimulus‐response curves and there is no threshold. Proof of tonic activity would require raising TAQ and observing if SAP fell (line Y, panel E) or stayed constant (line X). The clashed lines (DNX) (B and C) show the effect of arterial baroreceptor denervation on the gain (slope) of the chemoreflex.

Adapted from Rowell and Sheriff and Rowell and O'Leary
Figure 18. Figure 18.

Hypothetical stimulus–response curves (or baroreflex function curves) for the carotid sinus baroreflex. A, Important landmarks on the curves are defined (S marks point of saturation). Dashed line in panel A shows the gain or sensitivity of the reflex over the slope of the curve. Point of maximum gain is sometimes taken as putative baroreflex operating point. B, Illustrates decrease in the baroreflex gain or sensitivity (curve 1 to curve 2) in which operating point (OP) and systemic pressure are also shifted upward with no change in threshold. C, Shows upward shift in response (systemic pressure) with no change in threshold, gain, OP, or saturation point (S) of the baroreflex. D, shows a shift in threshold and OP to a higher carotid sinus and systemic pressure; this is the classical picture of so‐called baroreceptor resetting.

Adapted from Korner and reproduced from Rowell with permission
Figure 19. Figure 19.

A, Carotid sinus baroreflex stimulus – response curves at rest and levels of dynamic exercise (cycling) requiring 25%–75% of . Calculated carotid sinus transmural pressure was increased or decreased by 20 s applications of pulsatile negative or positive neck collar pressure applied at each ECG R wave and lasting 500–200 ms (at each calculated sinus pressure) depending on HR. Data were best described by linear fit with no difference in slope among rest and the levels of exercise. Dashed line connects prevailing systemic arterial and carotid sinus pressures (no external neck pressure) at rest and exercise.

Adapted from Papelier et al. .] B, Responses (as in A) to changes in neck collar pressures steadily applied for 5 s periods during rest and dynamic exercise requiring 25% and 50% of peak . Intersection of dashed line with curves shows prevailing pressure at rest and 50% peak exercise; prevailing pressure was taken as the operating point. Fitting of curves to logistic function provided threshold and saturation levels and supported the conclusion that the baroreflex had been “reset” by exercise. [Adapted from Potts et al. with permission
Figure 20. Figure 20.

Hypothetical baroreflex–function curves illustrate contrasting effects of central command and muscle chemoreflexes on curve position and operating points. Function curves can be expressed as the relationship between systemic arterial pressure (BP) and sympathetic nervous activity (SNA) or as carotid sinus pressure *(CSP) substituted for BP on the × axis vs. systemic arterial pressure *(BP), substituted for SNA on the y axis. A, In theory, central command “resets” the baroreflex to OP2 by acting on the neuron pool receiving baroreceptor afferents. The vertical dashed arrow from OP, (initial operating point) to the reset curve shows that any perturbation of pressure around the original OP is poorly corrected because this pressure falls on the least sensitive region of the new curve (i.e., the baroreflex appears momentarily insensitive at the onset of exercise). B, A vertical shift in the baroreflex function curve signifies that the muscle chemoreflex could raise BP or SNA without changing OP because the stimulus acts only on the efferent arm of the reflex and not the central neurons controlling the reflex. A + B illustrates the combined predicted effects of both stimuli on the baroreflex—function curve during exercise.

From Rowell and O'Leary with permission
Figure 21. Figure 21.

Evidence for stepwise “resetting” of the arterial baroreflex with graded increases in work intensity. Responses are from intact dogs (left) and after denervation of aortic baroreceptors (AO) and surgical isolation of carotid sinuses, with sinus pressure maintained constant at “resting” level. In dogs with isolated sinuses, HR and cardiac output rose normally, but elevations in SAP were extreme. After an initial rise in total vascular conductance between rest and exercise at 0% grade, total vascular conductance increased little thereafter with work intensity because of intense vasoconstriction, largely in working muscle. “Resting” carotid sinus pressure must have been interpreted centrally as a hypotensive stimulus that became greater with work intensity as a result of stepwise resetting of the baroreflex.

From Walgenbach and Donald , with permission from the American Heart Association
Figure 22. Figure 22.

Further evidence that onset of exercise shifts arterial baroreflex operating point to higher pressures. Delaying the rise in arterial pressure (in rabbits) during exercise by infusing nitroglycerin (C) markedly increased renal sympathetic nerve activity (A) and also heart rate. B and D, The exaggerated increases in sympathetic outflow and heart rate at any given arterial pressure when the rise in pressure was delayed by nitroglycerin.

Redrawn from DiCarlo and Bishop and reproduced from Rowell with permission
Figure 23. Figure 23.

Schematic representation of control of skin blood flow via thermoregulatory and nonthermoregulatory reflex control of vasoconstrictor (VC) and vasodilator (VD) outflow to skin. Thermoregulatory reflexes turn vasoconstriction and active vasodilation on (or off). Traditionally, nonthermoregulatory reflexes were thought to modulate only vasoconstrictor tone, but current evidence also indicates inhibition (−) of active vasodilation as well .

From Rowell with permission
Figure 24. Figure 24.

Increase in vasodilator threshold (rise in skin vascular conductance) from ∼37°C at rest to 37.2°C during moderate exercise. Open squares are normal skin at rest; solid circles are normal skin at exercise; open triangles are for skin with sympathetic adrenergic blockade by bretylium tosylate.

Adapted from Kellogg et al.
Figure 25. Figure 25.

Influence of lower body negative pressure (LBNP) on forearm blood flow (FBF) (open circles) and esophageal temperature (solid circles) during supine dynamic leg exercise. Data are from one representative experiment.

From Mack et al. with permission


Figure 1.

Right atrial and pulmonary wedge pressures during seated rest and five levels of upright dynamic leg exercise (cycling). Note relationship between wedge and right atrial pressure and abrupt rise in both pressures at peak exercise.

Adapted from Reeves et al. with permission


Figure 2.

Abrupt rise in mean right atrial (R.A.) pressure at onset of upright treadmill exercise. Sudden return of blood to the heart by skeletal muscle pump transiently exceeds left ventricular output [mean brachial arterial pressure (B.A.) also shown].

Adapted from Robinson et al.


Figure 3.

A, Relationship between left atrial pressure (LA) and left ventricular (LV) segment length at end‐diastole in one pig at 1 day (1d) and 8 days (8d) after thoracotomy without (solid circles) and with (open circles) pericardiectomy. B, Average stroke volumes before (open bars, N) and after (hatched bars, P) pericardiectomy. Data averaged from five pigs during three levels of treadmill exercise shown as percentage grade at 80–91 m/min.

Adapted from Hammond et al. with permission


Figure 4.

Effects of changing cardiac output by ventricular pacing on right atrial pressure in supine human subjects during rest (open circles) and exercise (cycling) (solid circles) [From Bevegard et al. .] Results were similar to those of Sheriff et al. on resting and exercising dogs (see Chapter ). Increments in cardiac output at rest caused by raising skin blood flow [Rest + Heat (solid triangles) from Rowell ], or further increments in cardiac output during exercise also caused by raising skin blood flow [Exercise + Heat (solid squares) from Rowell et al. ] also reduced right atrial pressure in proportion to the rise in cardiac output. Slopes during heating with and without exercise were obtained from different subjects in separate studies.



Figure 5.

Schematic illustration of the pressure profile across the vascular system. Up to the capillaries pressure oscillations characterize only the changing magnitudes of pulse pressure and not cardiac frequency. The circuit is broken in the muscle by the muscle pump, and pressure oscillations show external effects of muscle pumping and then respiratory pumping—four pumps in series. Blood flow from the left ventricle to the muscle is determined by the pressure difference between the heart and some unknown point in the muscle, whereas blood flow from active muscle to the right ventricle is determined by the force provided by the muscle pump.

Reproduced from Rowell with permission


Figure 6.

Summary of human sympathetic responses to mild to maximal dynamic exercise. Response pattern was unaffected by ambient temperature, active muscle mass, or physical conditioning . Sympathetic nervous activity begins to rise when vagal withdrawal is nearly complete and heart rate approaches 100 bpm. The indices of increased SNA are splanchnic and renal vasoconstriction (decline in RBF and SBF), increased plasma norepinephrine (NE) concentration, and plasma renin activity (PRA). Cutaneous, coronary, and skeletal muscle arterioles also constrict, suggesting diffuse sympathetic outflow. Also, MSNA (burst frequency) rises with HR up to near maximal values (see Fig. ). Lactic acid (HLa) does not rise until HR reaches 130–140 bpm (50%–60% of VO2max) or much higher in athletes.

Adapted from Rowell and O'Leary


Figure 7.

Renal neurohormonal responses to graded dynamic exercise (supine posture) in eight normal young humans. Exercise levels were 69, 132, and 188 W. Arteriovenous differences across the kidney (left column) and renal overflows (right column) of norepinephrine, immunoreactive neuropeptide Y, renin, and dopamine are related to the average heart rates during exercise. The renal arteriovenous differences for angiotensin (lower left) and also for epinephrine (not shown) were positive, showing net renal uptake of these hormones. The average values for renal blood flow at the three heart rates fall on the regression line for RBF vs. HR shown in Figure . Note the similar response pattern among all indices of RSNA.

Redrawn from Tidgren et al. and reproduced from Rowell with permission


Figure 8.

During 20 min of moderately heavy (65% of maximal workrate) leg exercise (upright cycling), HR, plasma NE concentration, and NE spillover rate rose continuously, whereas NE clearance was reduced slightly and significantly only at 30 min . *P < 0.05 compared with resting and P < 0.05 compared with 5 min exercise value. The increments in plasma NE and NE spillover are probably associated with the decline in mean arterial pressure (MAP).

From Leuenberger et al. with permission


Figure 9.

Muscle sympathetic nerve activity (MSNA) in resting legs increases in proportion to intensity of dynamic arm exercise (cycling). Data are unillustrated from a subject‐coauthor studied by Victor et al. . This subject could exercise at 80 W before body motion made microneuro‐graphic measurements of MSNA from a peroneal nerve impossible. Two important features are (1) there was a threshold for the rise in MSNA at 40 W (for all subjects), and (2) the delay in the rise in MSNA decreased with increasing work intensity and may have been almost absent at 80 W.

From original data kindly provided by D. R. Seals and reproduced from Rowell with permission


Figure 10.

A, Relationship between MSNA (expressed as Δburst frequency from the median nerve) and percentage of during dynamic leg exercise (cycling) at approximately 20%, 40%, 60%, and 75% . Disagreement with interpretation of Saito et al. is revealed by two sets of regression lines: dashed line by Saito et al., solid line by us. The ΔMSNA was calculated from “baseline” values (Δ = 0) that had been elevated by orthostatic stress (seated upright rest). Mild exercise and muscle pump restored CVP and aortic pulse pressure, thus lowering MSNA to supine resting values. MSNA appeared not to rise until work required 40% (rising solid line) (horizontal solid line illustrates our assumption that the slope of MSNA response is zero below 40% ). B, Relationship between MSNA and HR based on our interpretation (solid lines) is consistent with other findings and with Figure [see also Victor et al. ]. Dashed line of Saito et al. shows no HR threshold for MSNA.

Adapted from Saito et al.


Figure 11.

Differential responses to lumbar sympathetic nerve stimulation during rest and maximal contractions of rat gastrocnemius‐plantaris and soleus muscles. During contractions of the gastrocnemius‐plantaris, sympathetic stimulation had no effect on femoral vascular conductance so that blood flow rose passively with a sympathetically mediated rise in SAP. Vasoconstriction was prevented by the dominance of metabolite‐sensitive α2‐adrenoceptors in this glycolytic muscle. Conversely, the dominance of metabolite‐insensitive α1‐adrenoceptors in oxidative soleus muscle is revealed in the maintained vasoconstriction and fall in femoral vascular conductance during sympathetic stimulation combined with muscle contraction. A potential problem in interpreting these results is noted in the text.

From Thomas et al. with permission


Figure 12.

Evidence showing sympathetic modulation of both muscle blood flow and in rhythmically contracting human forearm muscles. A, Forearm blood flow (FBF) before (open circles) and after (solid circles) stellate ganglion block, measured as changes from resting flow before and after nerve block. B, Forearm (from calculated arterial and measured deep venous O2 contents and FBF) also rose with higher forearm blood flow, suggesting that had also been depressed by tonic SNA before blockade. *P < 0.05.

Adapted from Joyner et al. with permission


Figure 13.

Influence of autonomic blockade (hexamethonium + atropine) on the hemodynamic responses to mild treadmill exercise in dogs. Despite the maintenance of normal cardiac output by ventricular pacing (after ∼30 s), arterial pressure fell to 55 mm Hg during mild treadmill exercise after autonomic blockade (solid circles). Total vascular conductance (and hindlimb vascular conductance, not shown) continued to rise 60 s after blockade. Conversely, conductance fell after reaching a peak near 10 s when sympathetic nerves were not blocked (open circles).

From Sheriff et al. with permission


Figure 14.

A, The volume of blood available to fill the heart depends on the distribution of blood flow between compliant (C1) and noncompliant (C2) circuits. In exercise, active muscle [noncompliant circuit (C2)] becomes another pump actively returning blood to the heart. Cardiac filling pressures are determined by effectiveness of muscle pumping and sympathetic control of other circuits (e.g., C1); that is, in effect the ratios of blood flows through C1 and C2. B, The relationship between venous volume and blood flow in a compliant (C1) region (e.g., splanchnic or skin) and a noncompliant region (C2) (e.g., muscle). Line C2 shows no increase in venous volume with increased perfusion of resting muscle. Dashed line with arrow shows that muscle pump (MP) reduces venous volume.

Adapted from Rowell with permission


Figure 15.

A scheme for coordination of feedforward and feedback control of the cardiovascular system during exercise. Motor system signals used to initiate locomotion initiate feedforward actions (central command) on the cardiovascular system. Coordination with feedback control (the arterial baroreflex) is accomplished by sending the feedforward command to the feedback controller, which resets the operating point for arterial pressure regulation during exercise.

Adapted from Houk and reproduced from Rowell with permission


Figure 16.

Schematic illustration to demonstrate relative responses to central command (CC), muscle chemoreflex (CR), and muscle mechanoreflex (MR) during a powerful isometric contraction. A, Normal rise in arterial pressure is achieved initially by CC and some MR component. After about 1 min, CR may contribute to rise in pressure. Time course of CR is derived from ΔMSNA (arbitrary units) in bottom panel. Vascular occlusion (Occl.) of active limb at end of contraction prevents normal recovery (NR) of pressure. This is the test for a muscle chemoreflex. Pressure drops approximately 50% when CC ceases and is kept elevated by CR as long as ischemia persists. B, Heart rate is raised by CC (some MR?) via vagal withdrawal. C, MSNA is presumably increased by CR and remains elevated during post‐exercise ischemia (shaded region reveals variations in response).

Adapted from Rowell and O'Leary


Figure 17.

Schematic illustration of responses to the muscle chemoreflex during mild and moderate dynamic exercise. A, Mild exercise. Graded partial occlusions of the terminal aorta of an exercising dog generate graded decrements in terminal aortic flow (TAQ) and femoral arterial pressure, but arterial pressure (SAP) will not rise, and TAQ will not be partially restored until the chemoreflex becomes active—which happens at the second through fourth occlusions. The rise in SAP causes an ∼50% recovery of TAQ and femoral arterial pressure. B and C, Stimulus–response curves for the chemoreflex show that the reflex has a threshold (T). “Prevailing” TAQ (F, in panel B) and femoral arterial pressure (P, in panel C) represent their normal operating levels in exercise—which are on the flat (low‐gain) parts of the curves. Therefore, the chemoreflex is not tonically active and SAP does not rise until TAQ and/or femoral arterial pressure fall below some critical level (at T). D, Moderate dynamic exercise. Shows characteristic responses of a tonically active muscle chemoreflex. E and F show prevailing TAQ and P are on (or just at) the steep (high‐gain) portion of the stimulus‐response curves and there is no threshold. Proof of tonic activity would require raising TAQ and observing if SAP fell (line Y, panel E) or stayed constant (line X). The clashed lines (DNX) (B and C) show the effect of arterial baroreceptor denervation on the gain (slope) of the chemoreflex.

Adapted from Rowell and Sheriff and Rowell and O'Leary


Figure 18.

Hypothetical stimulus–response curves (or baroreflex function curves) for the carotid sinus baroreflex. A, Important landmarks on the curves are defined (S marks point of saturation). Dashed line in panel A shows the gain or sensitivity of the reflex over the slope of the curve. Point of maximum gain is sometimes taken as putative baroreflex operating point. B, Illustrates decrease in the baroreflex gain or sensitivity (curve 1 to curve 2) in which operating point (OP) and systemic pressure are also shifted upward with no change in threshold. C, Shows upward shift in response (systemic pressure) with no change in threshold, gain, OP, or saturation point (S) of the baroreflex. D, shows a shift in threshold and OP to a higher carotid sinus and systemic pressure; this is the classical picture of so‐called baroreceptor resetting.

Adapted from Korner and reproduced from Rowell with permission


Figure 19.

A, Carotid sinus baroreflex stimulus – response curves at rest and levels of dynamic exercise (cycling) requiring 25%–75% of . Calculated carotid sinus transmural pressure was increased or decreased by 20 s applications of pulsatile negative or positive neck collar pressure applied at each ECG R wave and lasting 500–200 ms (at each calculated sinus pressure) depending on HR. Data were best described by linear fit with no difference in slope among rest and the levels of exercise. Dashed line connects prevailing systemic arterial and carotid sinus pressures (no external neck pressure) at rest and exercise.

Adapted from Papelier et al. .] B, Responses (as in A) to changes in neck collar pressures steadily applied for 5 s periods during rest and dynamic exercise requiring 25% and 50% of peak . Intersection of dashed line with curves shows prevailing pressure at rest and 50% peak exercise; prevailing pressure was taken as the operating point. Fitting of curves to logistic function provided threshold and saturation levels and supported the conclusion that the baroreflex had been “reset” by exercise. [Adapted from Potts et al. with permission


Figure 20.

Hypothetical baroreflex–function curves illustrate contrasting effects of central command and muscle chemoreflexes on curve position and operating points. Function curves can be expressed as the relationship between systemic arterial pressure (BP) and sympathetic nervous activity (SNA) or as carotid sinus pressure *(CSP) substituted for BP on the × axis vs. systemic arterial pressure *(BP), substituted for SNA on the y axis. A, In theory, central command “resets” the baroreflex to OP2 by acting on the neuron pool receiving baroreceptor afferents. The vertical dashed arrow from OP, (initial operating point) to the reset curve shows that any perturbation of pressure around the original OP is poorly corrected because this pressure falls on the least sensitive region of the new curve (i.e., the baroreflex appears momentarily insensitive at the onset of exercise). B, A vertical shift in the baroreflex function curve signifies that the muscle chemoreflex could raise BP or SNA without changing OP because the stimulus acts only on the efferent arm of the reflex and not the central neurons controlling the reflex. A + B illustrates the combined predicted effects of both stimuli on the baroreflex—function curve during exercise.

From Rowell and O'Leary with permission


Figure 21.

Evidence for stepwise “resetting” of the arterial baroreflex with graded increases in work intensity. Responses are from intact dogs (left) and after denervation of aortic baroreceptors (AO) and surgical isolation of carotid sinuses, with sinus pressure maintained constant at “resting” level. In dogs with isolated sinuses, HR and cardiac output rose normally, but elevations in SAP were extreme. After an initial rise in total vascular conductance between rest and exercise at 0% grade, total vascular conductance increased little thereafter with work intensity because of intense vasoconstriction, largely in working muscle. “Resting” carotid sinus pressure must have been interpreted centrally as a hypotensive stimulus that became greater with work intensity as a result of stepwise resetting of the baroreflex.

From Walgenbach and Donald , with permission from the American Heart Association


Figure 22.

Further evidence that onset of exercise shifts arterial baroreflex operating point to higher pressures. Delaying the rise in arterial pressure (in rabbits) during exercise by infusing nitroglycerin (C) markedly increased renal sympathetic nerve activity (A) and also heart rate. B and D, The exaggerated increases in sympathetic outflow and heart rate at any given arterial pressure when the rise in pressure was delayed by nitroglycerin.

Redrawn from DiCarlo and Bishop and reproduced from Rowell with permission


Figure 23.

Schematic representation of control of skin blood flow via thermoregulatory and nonthermoregulatory reflex control of vasoconstrictor (VC) and vasodilator (VD) outflow to skin. Thermoregulatory reflexes turn vasoconstriction and active vasodilation on (or off). Traditionally, nonthermoregulatory reflexes were thought to modulate only vasoconstrictor tone, but current evidence also indicates inhibition (−) of active vasodilation as well .

From Rowell with permission


Figure 24.

Increase in vasodilator threshold (rise in skin vascular conductance) from ∼37°C at rest to 37.2°C during moderate exercise. Open squares are normal skin at rest; solid circles are normal skin at exercise; open triangles are for skin with sympathetic adrenergic blockade by bretylium tosylate.

Adapted from Kellogg et al.


Figure 25.

Influence of lower body negative pressure (LBNP) on forearm blood flow (FBF) (open circles) and esophageal temperature (solid circles) during supine dynamic leg exercise. Data are from one representative experiment.

From Mack et al. with permission
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Loring B. Rowell, Donal S. O'Leary, Dean L. Kellogg. Integration of Cardiovascular Control Systems in Dynamic Exercise. Compr Physiol 2011, Supplement 29: Handbook of Physiology, Exercise: Regulation and Integration of Multiple Systems: 770-838. First published in print 1996. doi: 10.1002/cphy.cp120117