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¹ Graduate School of Human Sciences² Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, Japan

	Abstract

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Our previous studies showed that venous occlusion or passive stretch of the lower limb, assuming a mechanical stimulus, attenuates the vasoconstriction in the non-exercised forearm during postexercise muscle ischaemia (PEMI) of the upper limb. In this study, we investigated whether a metabolic stimulus to the lower limb induces a similar response. Eight subjects performed a 2 min static handgrip exercise at 30% maximal voluntary contraction (MVC) followed by 3 min PEMI of the upper limb, concomitant with or without 2 min static ankle dorsiflexion at 30% MVC followed by 2 min PEMI of the lower limb. During PEMI of the upper limb alone, forearm blood flow (FBF) and forearm vascular conductance (FVC) in the non-exercised arm decreased significantly, whereas during combined PEMI of the upper and lower limbs, the decreases in FBF and FVC produced by PEMI of the upper limb was attenuated. Forearm blood flow and FVC were significantly greater during combined PEMI of the upper and lower limbs than during PEMI of the upper limb alone. When PEMI of the lower limb was released after combined PEMI of the upper and lower limbs (only PEMI of the upper limb was maintained continuously), the attenuated decreases in FBF and FVC observed during combined PEMI of the upper and lower limbs was not observed. Thus, forearm vascular responses differ when muscle metaboreceptors are activated in the upper limb and when there is combined activation of muscle metaboreceptors in both the upper and lower limbs.

(Received 13 February 2006; accepted after revision 24 April 2006; first published online 27 April 2006)
Corresponding author I. Muraoka: Faculty of Sport Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama, Japan 359-1192. Email: imuraoka{at}waseda.jp

	Introduction

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The exercise pressor reflex is a feedback mechanism that, via the activation of muscle afferents (group III and IV) through medullary pathways, activates the sympathetic nervous system and evokes increases in arterial pressure (AP), heart rate (HR) and vasoconstriction in non-active tissues (Mitchell et al. 1983). Two types of information within active skeletal muscle, mechanical and metabolic, are believed to be conducted by muscle afferents (Kumazawa & Mizumura, 1977; Kaufman & Rybicki, 1987).

In humans, each mechanical and metabolic stimulus in skeletal muscle differentially affects the cardiovascular response. Mechanical stimuli elicited via muscle stretch increase HR without any change in AP (Gladwell & Coote, 2002; Gladwell et al. 2005), whereas metabolic stimuli produced by postexercise muscle ischaemia (PEMI) evoke increases in AP, muscle sympathetic nerve activity (MSNA) and vascular resistance in non-active tissues, with little change in HR (Alam & Smirk, 1937; Rusch et al. 1981; Mark et al. 1985). In these studies, each mechanical and metabolic stimulus was applied to a single limb muscle. However, the mechanism by which cardiovascular responses are regulated in the situation where muscular stimuli are applied to multiple limbs has not been determined.

The cardiovascular responses to exercise performed by multiple limbs simultaneously amount to less than the algebraic sum of the responses produced separately by each limb (Bevegard et al. 1966; Stenberg et al. 1967; Savard et al. 1989). The responses of MSNA exhibit a similar relationship (Seals, 1989). It has been shown that, under certain circumstances, AP is reduced by adding leg exercise to arm exercise (Secher et al. 1977; Volianitis & Secher, 2002; Volianitis et al. 2003, 2004). These data suggest that cardiovascular responses elicited during exercise of separate limbs exhibit an ‘inhibitory interaction’ (Seals, 1989).

Previous reports from our laboratory showed that venous occlusion (Tokizawa et al. 2004a) or passive stretch (Tokizawa et al. 2004b) of the lower limb, assuming only muscle afferent activation, inhibited vasoconstriction in the non-exercised forearm during PEMI of the upper limb. These results indicate that muscle afferent activation can inhibit the acceleration of cardiovascular responses, and were thought to be caused by the activation of mechanosensitive muscle afferents (muscle mechanoreceptors). However, it is unknown whether the inhibitory responses are interactive effects arising from the combined activation of muscle afferents from different limbs or are specifically evoked by muscle mechanoreceptor activation. It remains to be determined whether the activation of metabosensitive muscle afferents (muscle metaboreceptors) evokes these inhibitory responses. Therefore, in the present study, the aim was to determine whether muscle metaboreceptor activation in the lower limb attenuates forearm vasoconstriction during PEMI of the upper limb.

	Methods

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Subjects and preliminary testing

Eight men volunteered to participate in the present study (age, 24.4 ± 1.8 years; height, 172.1 ± 3.7 cm; and weight, 70.4 ± 9.1 kg; means ± S.D.). Before the experiment, the subjects were informed of all aspects of the study, and each signed an informed consent document. The study was approved by the local ethics committee; all work conformed to the requirements of the Declaration of Helsinki.

During a preliminary visit to the laboratory, maximal voluntary contraction (MVC) of handgrip (HG) and ankle dorsiflexion (DF) was assessed in the right hand and the right foot using an HG dynamometer and the Cybex isokinetic dynamometer (Lumex Inc., Ronkonkoma, NY, USA), respectively. The average of three attempts was taken as the subject's MVC. Additionally, the subjects were familiarized with the experimental procedures.

Study design

On a different day after the preliminary test, the subjects performed three trials in a random order on the same day. Intervals of more than 15 min were allowed between trials. The two main trials included 2 min HG and 3 min PEMI of the upper limb. Only this model was included in the control trial. In the combined trial, 2 min DF and 2 min PEMI of the lower limb were performed concurrently with 2 min HG and 2 min PEMI of the upper limb, respectively, to activate muscle metaboreceptors in the upper and lower limbs simultaneously (Fig. 1, phase A). After 2 min combined PEMI of the upper and lower limbs, the PEMI of the lower limb was released and only the PEMI of the upper limb was maintained continuously for 1 min to examine the influence of removal of muscle metaboreceptor activation in the lower limb (Fig. 1, phase B). To confirm activation of muscle metaboreceptor in the lower limb only, 2 min DF and 2 min PEMI of the lower limb alone were performed.

View larger version (13K): [in this window] [in a new window]   Figure 1.  Schematic representation of experimental protocol in the control and combined trials During phase A (2–4 min), the purpose of comparing ‘Arm–Metaboreceptor’ of the control trial with ‘Arm & Calf–Metaboreceptor’ of the combined trial is to examine the influence of lower limb metaboreceptor activation. During phase B (4–5 min), the purpose of comparing ‘Arm–Metaboreceptor’ of the control trial with ‘Arm–Metaboreceptor’ of the combined trial is to examine the influence of removal of lower limb metaboreceptor activation

Measurements

Arterial pressure was measured with a finger cuff using an optomechanical photoplethysmographic method (2300 Finapres, Ohmeda, Englewood, CO, USA). The monitoring finger cuff was placed around the middle finger of the left hand and supported at the heart level. Heart rate was determined using standard electrocardiography leads (model OEC-8108, Nihon Kohden, Tokyo, Japan). The resting values of AP and HR were determined by averaging data collected over 2 min immediately before the onset of exercise. During exercise and PEMI, the averaged values were calculated from data collected during the final 10 s of every 30 s section. Forearm blood flow (FBF) in the non-exercised arm was measured by venous occlusion plethysmography (Whitney, 1953) using a mercury-in-silastic strain gauge (model EC-5R, Hokanson, Bellevue, WA, USA). The strain gauge was placed around the largest circumference of the left forearm. The arm was supported at the level of the heart, and a venous occlusion pressure of 60 mmHg was applied. The average of three measurements was taken as the baseline value. During exercise and PEMI, FBF was measured at 30 s intervals. The FBF value was calculated from the rate of increase of forearm volume during venous occlusion and expressed as millilitres per 100 ml of forearm volume per minute. Forearm vascular conductance (FVC) in the non-exercised arm was calculated as FBF (in ml (100 ml)^–1 min^–1) divided by mean AP (MAP; in mmHg), and was expressed in ‘units’ (actual units, ml (100 ml)^–1 min^–1 mmHg^–1). Although the target limb is usually slightly elevated above heart level in venous occlusion plethysmography to ensure venous drainage, we measured it at heart level because AP was measured simultaneously in the same arm. We previously confirmed that the FBF value measured at heart level correlated significantly with that measured above heart level (Tokizawa et al. 2004b). Furthermore, although hand occlusion is usually applied to isolate hand circulation in venous occlusion plethysmography, we measured it without hand occlusion because AP was measured simultaneously in the same arm. It has been reported that hand occlusion is not necessary for accurate flow measurements in the forearm during and after static exercise (Williams & Lind, 1979).

In an additional experiment on three subjects, myoelectric activity of flexor carpi radialis muscles in the non-exercised arm was detected in the control and combined trials using surface electromyography and recorded using bipolar 5-mm-diameter Ag–AgCl electrodes with an interelectrode distance of 40 mm. Signals were amplified by a bioelectric amplifier (model AB-621G, Nihon Kohden, Tokyo, Japan) and collected by Powerlab (ADInstruments, Castle Hill, NSW, Australia). At the same time, skin blood flow in the non-exercised forearm was measured as laser Doppler flow (LDF; model ALF21, Advance, Tokyo, Japan). The LDF probe was attached to the skin at the largest area of the non-exercised forearm.

Statistics

A repeated-measures two-way analysis of variance (ANOVA), with trial and time as the main effects, was used to determine significant differences. If a significant F value was observed, Fisher's post hoc test was used to locate the difference. Statistical significance was accepted at P < 0.05. Values are expressed as means ± S.E.M.

	Results

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Figure 2 shows cardiovascular responses in the DF-only trial. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), MAP and HR increased significantly and FVC decreased significantly during exercise. During PEMI of the lower limb, SAP, DAP and MAP were maintained at a significantly elevated level relative to the resting values. FBF and FVC decreased significantly during PEMI of the lower limb (except for FBF at 2.5 min, P = 0.07; at 4.0 min, P = 0.15). After the release of PEMI of the lower limb, each parameter immediately returned to the resting values.

View larger version (23K): [in this window] [in a new window]   Figure 2.  Systolic arterial pressure (SAP; A), diastolic arterial pressure (DAP; B), mean arterial pressure (MAP; C), heart rate (HR; D), forearm blood flow (FBF; E) and forearm vascular conductance (FVC; F) in the DF-only trial DF, dorsiflexion; PEMI, postexercise muscle ischaemia. Values are means ± S.E.M. * Significantly different from rest (P < 0.05)

View larger version (22K): [in this window] [in a new window]   Figure 3.  Systolic arterial pressure (SAP; A), diastolic arterial pressure (DAP; B), mean arterial pressure (MAP; C) and heart rate (HR; D) in each control and combined trial HG, handgrip; DF, dorsiflexion; PEMI, postexercise muscle ischaemia. Values are means ± S.E.M. * Significantly different from control trial (P < 0.05)

View larger version (19K): [in this window] [in a new window]   Figure 4.  Forearm blood flow (FBF; A) and forearm vascular conductance (FVC; B) in each control and combined trial Inset in A shows skin blood flow in the non-exercised forearm in each control and combined trial. HG, handgrip; DF, dorsiflexion; PEMI, postexercise muscle ischaemia. Values are means ± S.E.M. * Significantly different from control trial (P < 0.05)

	Discussion

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The major findings of this study are that no decreases in FBF or FVC during PEMI of the upper limb were observed with PEMI of the lower limb, and that subsequent removal of PEMI from the lower limb induced similar FBF and FVC responses to those observed during PEMI of the upper limb. This indicates that forearm vascular responses differ when muscle metaboreceptors are activated in the upper limb and when there is combined activation of muscle metaboreceptors in both the upper and lower limbs.

During physical exercise, the brain cardiovascular centres receive neural inputs from higher brain centres (central command) and contracting muscles (exercise pressor reflex). They then integrate these inputs and determine adequate neural efferent outflow. It is known that simultaneous activation of central command and the exercise pressor reflex evokes cardiovascular responses that sum non-algebraically (Waldrop et al. 1986; Rybicki et al. 1989). The response evoked by activating both mechanisms simultaneously is significantly less than the sum of the responses evoked by each mechanism separately. Furthermore, especially during exercise performed simultaneously by multiple limbs, the muscle afferent inputs from each limb may be involved in an inhibitory interaction in the cardiovascular centres other than those of central command.

The external cuff pressure of PEMI causes accumulation of metabolites in the exercised limb (Alam & Smirk, 1937), which activates muscle metaboreceptors in the absence of central command and muscle mechanoreceptor activation. In the present study, AP increased significantly, and FBF and FVC decreased significantly, during PEMI of the upper limb in the control trial and during PEMI of the lower limb in the DF-only trial, suggesting that each PEMI model fully activated muscle metaboreceptors. According to a previous study (Saito, 1995), MSNA should be increased during each PEMI. However, FBF did not differ from the resting value during combined PEMI of the upper and lower limbs in the combined trial. Forearm vascular conductance was significantly higher during combined PEMI of the upper and lower limbs in the combined trial than during PEMI of the upper limb in the control trial. Furthermore, in the combined trial during PEMI of 4–5 min, thigh cuff deflation after combined PEMI of the upper and lower limbs (PEMI of the upper limb was maintained) evoked a decrease in FBF. No significant difference was observed in FBF or FVC between the control and combined trials during PEMI of 4–5 min. That is, no attenuated decreases in FBF and FVC were observed after the removal of PEMI of the lower limb. The release of PEMI of the lower limb immediately returned AP, FBF and FVC to the resting values in the DF-only trial, which suggests that muscle metaboreceptor activation was withdrawn immediately after the removal of PEMI of the lower limb. These results indicate that the forearm vascular responses to combined muscle metaboreceptor activation in both the upper and lower limbs differ from responses to the activation of muscle metaboreceptors in the upper limb only.

In cardiovascular regulation, as well as the feedback mechanism arising from active muscle, a feedback mechanism related to the central baroreceptor is involved, i.e. the carotid sinus baroreflex and cardiopulmonary baroreflex. Arterial pressure tended to increase more in the combined than in the control trial during PEMI of 2–4 min but not during exercise. Although the difference was not significant, the carotid sinus baroreceptor stimulus would differ between trials, and which could operate in the combined trial. The cardiopulmonary baroreflex vigorously affects forearm vasculature. Because we did not measure central venous pressure, we cannot completely exclude the possibility that the cardiopulmonary baroreflex operated in the combined trial. Heart rate was significantly increased during PEMI of the lower limb in the DF-only trial, and was greater during combined PEMI of the upper and lower limbs than during PEMI of the upper limb alone. These effects could be cardiopulmonary baroreceptor-mediated increases arising from reduction of venous return. However, unloading the cardiopulmonary baroreceptor decreases FVC (Johnson et al. 1974) and has no effect on the sensitivity of the vasomotor carotid sinus baroreflex response during exercise (Potts et al. 1995). Therefore the cardiopulmonary baroreflex is not the main determinant of attenuated decreases in FBF and FVC in the combined trial.

Because the neural input from higher brain centres and exercising muscles was greater in the combined trial than in the control trial, it is plausible that, during exercise, the output response is greater in the combined trial. However, in the present study, although the HR response was significantly greater in the combined trial than in the control trial during exercise, the AP response was similar between the control and combined trials. It has been reported that adding leg exercise to arm exercise reduces MAP, whereas HR is higher during combined arm and leg exercise than during arm exercise alone (Secher et al. 1977; Volianitis & Secher, 2002; Volianitis et al. 2003, 2004). Although we can only speculate on the possible mechanisms involved, these uncoupled HR and AP responses might reflect differences between the control of sympathetic outflow to each of the tissues (Dampney, 1994) and between cardiac vagal and sympathetic outflow (Murata & Matsukawa, 2001).

The sympathetic nervous system controls the skin and muscle vascular responses differently. Skin and muscle sympathetic nerve activities are differentially affected during exercise and PEMI (Vissing et al. 1991; Silber et al. 1998). Although FBF measured by venous occlusion plethysmography reflects both skin and muscle blood flow, we found no changes in skin blood flow in the non-exercised forearm (measured by laser Doppler flowmetry). Therefore, the attenuated decrease in FBF in the combined trial is probably attributable to changes in muscle blood flow.

Although we found attenuation of the decreases in FBF and FVC in the combined trial, we could not evaluate the vasoactive mechanism. Because FBF and FVC were measured in the non-exercised limb with no EMG activity, exercise-induced metabolic vasocontrol was not involved. Furthermore, exercised-induced byproducts do not circulate to the other organs of the body during PEMI, which argues against a contribution from a circulating vasodilatory substance. Therefore, attenuation of sympathetic vasoconstriction, acceleration of local vasodilatation, and shear stress are possible mechanisms for the attenuated decreases in FBF and FVC. The resolution of the vasoactive mechanism awaits direct recording of MSNA from the peroneal nerve and use of a pharmacological approach.

Surprisingly, HR increased significantly during PEMI of the lower limb in the DF-only trial. Thigh cuff occlusion blocked vascular beds substantially more than did upper-arm cuff occlusion, resulting in the loss of vascular conductance in that leg and reduction of venous return. Furthermore, thigh cuff occlusion increased the intramuscular pressure over a more widespread area in the leg than did upper-arm cuff occlusion, which could have elicited greater activation of the muscle mechanoreceptors. Although we can only speculate, these would be factors involved in the elevation of HR during PEMI of the lower limb.

In conclusion, the present study showed that PEMI of the lower limb attenuated the decreases in FBF and FVC induced by PEMI of the upper limb, thereby suggesting that the forearm vascular responses to combined muscle metaboreceptor activation in both the upper and lower limbs differ from responses to the activation of muscle metaboreceptors in the upper limb only.

	References

Top Abstract Introduction Methods Results Discussion References

 
Alam M & Smirk FH (1937). Observations in man upon a blood pressure raising reflex arising from the voluntary muscles. J Physiol 89, 372–383.

Bevegard S, Freyschuss U & Strandell T (1966). Circulatory adaptation to arm and leg exercise in supine and sitting position. J Appl Physiol 21, 37–46.[Free Full Text]

Dampney RA (1994). Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 74, 323–364.[Free Full Text]

Gladwell VF & Coote JH (2002). Heart rate at the onset of muscle contraction and during passive muscle stretch in humans: a role for mechanoreceptors. J Physiol 540, 1095–1102.[Abstract/Free Full Text]

Gladwell VF, Fletcher J, Patel N, Elvidge LJ, Lloyd D, Chowdhary S & Coote JH (2005). The influence of small fibre muscle mechanoreceptors on the cardiac vagus in humans. J Physiol 567, 713–721.[Abstract/Free Full Text]

Johnson JM, Rowell LB, Niederberger M & Eisman MM (1974). Human splanchnic and forearm vasoconstrictor responses to reductions of right atrial and aortic pressures. Circ Res 34, 515–524.[Abstract/Free Full Text]

Kaufman MP & Rybicki KJ (1987). Discharge properties of group III and IV muscle afferents: their responses to mechanical and metabolic stimuli. Circ Res 61, I60–I65.[Medline]

Kumazawa T & Mizumura K (1977). Thin-fibre receptors responding to mechanical, chemical, and thermal stimulation in the skeletal muscle of the dog. J Physiol 273, 179–194.[Abstract/Free Full Text]

Mark AL, Victor RG, Nerhed C & Wallin BG (1985). Microneurographic studies of the mechanisms of sympathetic nerve responses to static exercise in humans. Circ Res 57, 461–469.[Abstract/Free Full Text]

Mitchell JH, Kaufman MP & Iwamoto GA (1983). The exercise pressor reflex: its cardiovascular effects, afferent mechanisms, and central pathways. Annu Rev Physiol 45, 229–242.[CrossRef][Medline]

Murata J & Matsukawa K (2001). Cardiac vagal and sympathetic efferent discharges are differentially modified by stretch of skeletal muscle. Am J Physiol Heart Circ Physiol 280, H237–H245.[Abstract/Free Full Text]

Potts JT, Shi X & Raven PB (1995). Cardiopulmonary baroreceptors modulate carotid baroreflex control of heart rate during dynamic exercise in humans. Am J Physiol 268, H1567–H1576.[Medline]

Rusch NJ, Shepherd JT, Webb RC & Vanhoutte PM (1981). Different behavior of the resistance vessels of the human calf and forearm during contralateral isometric exercise, mental stress, and abnormal respiratory movements. Circ Res 48, I118–I130.[Medline]

Rybicki KJ, Stremel RW, Iwamoto GA, Mitchell JH & Kaufman MP (1989). Occlusion of pressor responses to posterior diencephalic stimulation and muscular contraction. Brain Res Bull 22, 305–312.[CrossRef][Medline]

Saito M (1995). Differences in muscle sympathetic nerve response to isometric exercise in different muscle groups. Eur J Appl Physiol 70, 26–35.[CrossRef]

Savard GK, Richter EA, Strange S, Kiens B, Christensen NJ & Saltin B (1989). Norepinephrine spillover from skeletal muscle during exercise in humans: role of muscle mass. Am J Physiol 257, H1812–H1818.

Seals DR (1989). Influence of muscle mass on sympathetic neural activation during isometric exercise. J Appl Physiol 67, 1801–1806.[Abstract/Free Full Text]

Secher NH, Clausen JP, Klausen K, Noer I & Trap-Jensen J (1977). Central and regional circulatory effects of adding arm exercise to leg exercise. Acta Physiol Scand 100, 288–297.[Medline]

Silber DH, Sutliff G, Yang QX, Smith MB, Sinoway LI & Leuenberger UA (1998). Altered mechanisms of sympathetic activation during rhythmic forearm exercise in heart failure. J Appl Physiol 84, 1551–1559.[Abstract/Free Full Text]

Stenberg J, Astrand PO, Ekblom B, Royce J & Saltin B (1967). Hemodynamic response to work with different muscle groups, sitting and supine. J Appl Physiol 22, 61–70.[Free Full Text]

Tokizawa K, Mizuno M, Nakamura Y & Muraoka I (2004a). Venous occlusion to the lower limb attenuates vasoconstriction in the nonexercised limb during posthandgrip muscle ischemia. J Appl Physiol 96, 981–984.[Abstract/Free Full Text]

Tokizawa K, Mizuno M, Nakamura Y & Muraoka I (2004b). Passive triceps surae stretch inhibits vasoconstriction in the nonexercised limb during posthandgrip muscle ischemia. J Appl Physiol 97, 1681–1685.[Abstract/Free Full Text]

Vissing SF, Scherrer U & Victor RG (1991). Stimulation of skin sympathetic nerve discharge by central command. Differential control of sympathetic outflow to skin and skeletal muscle during static exercise. Circ Res 69, 228–238.[Abstract/Free Full Text]

Volianitis S, Krustrup P, Dawson E & Secher NH (2003). Arm blood flow and oxygenation on the transition from arm to combined arm and leg exercise in humans. J Physiol 547, 641–648.[Abstract/Free Full Text]

Volianitis S & Secher NH (2002). Arm blood flow and metabolism during arm and combined arm and leg exercise in humans. J Physiol 544, 977–984.[Abstract/Free Full Text]

Volianitis S, Yoshiga CC, Vogelsang T & Secher NH (2004). Arterial blood pressure and carotid baroreflex function during arm and combined arm and leg exercise in humans. Acta Physiol Scand 181, 289–295.[CrossRef][Medline]

Waldrop TG, Mullins DC & Millhorn DE (1986). Control of respiration by the hypothalamus and by feedback from contracting muscles in cats. Respir Physiol 64, 317–328.[CrossRef][Medline]

Whitney RJ (1953). The measurement of volume changes in human limbs. J Physiol 121, 1–27.[Free Full Text]

Williams CA & Lind AR (1979). Measurement of forearm blood flow by venous occlusion plethysmography: influence of hand blood flow during sustained and intermittent isometric exercise. Eur J Appl Physiol 42, 141–149.[CrossRef]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tokizawa, K. Articles by Muraoka, I. Search for Related Content PubMed Articles by Tokizawa, K. Articles by Muraoka, I. Related Collections Cardiovascular control