Limb suction evoked during arterial occlusion causes systemic sympathetic activity in humans

Abstract

Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP). We hypothesized that the application of suction to the human limbs would activate this venous distension reflex and raise sympathetic outflow. We placed airtight pressure tanks and applied 100 mmHg negative pressure to an arterially occluded limb (occlusion and suction, O&S) to induce tissue deformation without fluid translocation. BP, heart rate (HR), and MSNA were assessed in 19 healthy subjects during 2 min of arm or leg O&S. Occlusion without suction served as a control. During a separate visit, saline (5% forearm volume) was infused into veins of the arterially occluded arm (n = 13). The O&S increased limb circumference, MSNA burst rate (arm: Δ6.7 ± 0.7; leg: Δ6.8 ± 0.7 bursts/min), and total activity (arm: Δ199 ± 14; leg: Δ172 ± 22 units/min) and BP (arm: Δ4.3 ± 0.3; leg: Δ9.4 ± 1.4 mmHg) from the baseline. The MSNA and BP responses during arm O&S correlated with those during leg O&S. Occlusion alone had no effect on MSNA and BP. MSNA (r = 0.607) responses during arm O&S correlated with those evoked by the saline infusion into the arm. These correlations suggest that sympathetic activation during limb O&S is likely, at least partially, to be evoked via the venous distension reflex. These data suggest that suction of an occluded limb evokes sympathetic activation and that the limb venous distension reflex exists in arms and legs of normal humans.

prior studies have shown that the distension of abdominal veins increases sympathetic efferent activity in rabbits (2) and dogs (12). Limb venous ligation evokes vasoconstriction in both the occluded and contralateral extremities in dogs (5). Evidence in animals suggests that afferent nerve endings in peripheral veins may sense regional blood volume changes and, in turn, contribute to the blood pressure (BP) regulation via a reflex response in cats (11, 21), rabbits (2), and dogs (12). Venous distension increases the discharge of group III and IV afferent nerves in cat hindlimbs (18).

Our recent reports (7–10) have shown that volume infusion (saline or albumin solution, 5% forearm volume, ∼50 ml) into the veins of an occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and BP in human subjects. The magnitude of the MSNA and BP responses depends on the volume and the rate of the infusate during arm vein distension (8). When lidocaine is added to the forearm infusate, the MSNA and BP responses to venous distension are abolished (9). These observations clearly suggest that limb venous distension evokes a sympathoexcitatory reflex (termed venous distension reflex) and, thus, increases BP in humans. Of note, a recent report by Yamauchi et al. (33) has shown this reflex is also present in rats. Additionally, we have shown that venous infusion of albumin evokes a larger and more sustained increase in MSNA and BP than those with infusion of equal volume of saline (9). Albumin is a potent intravascular oncotic agent, and, thus, for a given volume, infusion of albumin should cause more distension than is seen with saline. Thus, we speculate that the major determinant of the response we have noted is the deformation of the vessels and/or pressure gradient generated across the vessels. It should be noted that all of these data regarding the venous distension reflex in humans (7–10) and rats (33) were obtained with the volume infusion model. We speculate that it is necessary to develop a noninfusion approach to test the venous distension reflex.

When humans stand, blood is translocated into the lower body capacitance vessels, which raises the pressure gradient across the vessels, and the dependent lower limb veins become distended (15). Although it is widely accepted that cardiopulmonary and arterial baroreceptors are disengaged with standing, we speculate that venous distension reflex will be activated and will, thus, also contribute to BP control seen during an orthostatic challenge. We speculate that the role of venous distension reflex during standing is independent from the baroreflex. Thus, it is crucial to determine whether the venous distension reflex exists in human lower limbs when baroreceptors are not unloaded. Moreover, because the volume/mass of a lower limb is much larger than an upper limb, it was reasonable to speculate that the responses during the venous distension in a lower limb could be greater than those during the venous distension in an upper limb. We would like to emphasize that the classic experimental models (e.g., head up tilt or lower body negative pressure, LBNP) simultaneously increase the lower limb blood volumes and decrease the central blood volumes; thus, these models cannot be used to address this question. Thus, we developed the method in the present study. Previous studies in our group (19, 20) employed the suction of an unoccluded upper or lower limb with airtight pressure tanks to raise the transmural pressure. To avoid fluid shift from central to the treated limb, in the present study, we employed airtight pressure tanks to apply suction on an arterially occluded limb (occlusion and suction, O&S). This intervention decreases the surface pressure, and, thus, induces a radial pressure gradient from the center to the surface of the limb. In turn, we speculate that this would activate the venous distension reflex and raise MSNA.

METHODS

Subjects

Nineteen subjects (10 male, 9 female) participated in the study. The average age was 29 ± 2 (SE) yr, and all were of average height (171 ± 2 cm) and normal weight (70 ± 3 kg). All subjects were normotensive (supine BP <140/90 mmHg), in good health, and none were taking medications. Subjects refrained from caffeine, alcohol, and exercise for 24 h prior to the study. The experimental protocol was approved by the Institutional Review Board of the Milton S. Hershey Medical Center and conformed with the Declaration of Helsinki. Each subject had the purposes and risks of the protocol explained to them before written informed consent was obtained.

Measurements

Beat-by-beat BP was recorded from a finger of the nontreated arm (Finometer, Finapres Medical Systems, Amsterdam, The Netherlands) with resting values verified with an automated sphygmomanometer from the brachial artery (SureSigns VS3, Philips, Philip Medical System) of the nontreated arm. Heart rate (HR) was monitored from the electrocardiogram (Cardicap/5, Datex-Ohmeda; GE Healthcare, Princeton, NJ). Respiratory frequency was monitored using piezoelectric pneumography. Multifiber recordings of MSNA were obtained with a tungsten microelectrode inserted in the peroneal nerve of the nontreated leg. A reference electrode was placed subcutaneously 2–3 cm from the recording electrode. The recording electrode was adjusted until a site was found in which muscle sympathetic bursts were clearly identified using previously established criteria (28). The nerve signal was amplified, band-pass filtered with a bandwidth of 500-5,000 Hz, and integrated with a time constant of 0.1 s (Iowa Bioengineering, Iowa City, IA). The nerve signal was also routed to a loudspeaker and a computer for monitoring.

In the O&S protocol, the changes of limb circumference in the tank were estimated by mercury strain-gauge plethysmograph attached at the widest part of the forearm and calf with a standard pretension (14, 31). The gauges were calibrated in situ in each trial. To monitor the effects of the occlusion, skin blood flow probes of laser-Doppler flowmetry (MoorLab, Moor Instruments, Devon, UK) were placed on the limb in the tank and on the contralateral untreated (control) limb, respectively.

Protocols

Negative pressure on an occluded limb (O&S).

All subjects were tested in the supine position in a temperature-controlled room (∼23°C). The subject's nondominant forearm and ipsilateral leg were inserted into the airtight pressure tanks (19, 20). The lower aspect of the nondominant arm was sealed above the elbow, and the lower aspect of the ipsilateral leg was sealed above the knee with neoprene cuffs for sealing. Occlusion cuffs were placed over the upper arm and the thigh, respectively. It should be noted that there was a distance (∼10–15 cm) between the occlusion cuff and the tank. Thereafter, microneurography was performed on the contralateral untreated leg.

Although both the arm and the leg tanks were instrumented, the O&S was performed only on one limb (arm or leg) in each trial. In each trial, baseline data (5 min) were collected before the occlusion cuff on the upper arm/thigh was inflated to 250 mmHg. After ∼10 s, the limb tank was quickly (within 1 s) depressurized down to −100 mmHg for 2 min, after which the pressure in the tank and the cuff was released. The application of negative pressure that creates a suction effect on the limb, leads to an overall increase in pressure gradient across the limb. The intervention at this strength (i.e., −100 mmHg for 2 min) was chosen because it clearly raised the circumference of the limb without inducing pain or uncomfortable sensation. In the control trials, the occlusion cuff on the upper arm/thigh was inflated to 250 mmHg for ∼2 min, but the negative pressure was not applied on the tank (occlusion alone). During this occlusion-alone trial, the air pump was turned on to generate a similar background audio noise without applying the suction. The four trials of arm O&S, leg O&S, occlusion alone on the arm, and the occlusion alone on the leg were performed in a random order with intervals, during which, subjects rested for at least 15 min and until HR and BP returned to baseline. Subjects were blinded as to the trial order before the interventions were applied.

Volume infusion into an occluded arm.

This protocol was employed to determine whether the MSNA responses to O&S were evoked in a similar fashion as was the venous distension reflex seen during the volume infusion into an occluded forearm. This protocol was performed in 13 subjects during a separate visit. The details of this protocol have been described in our previous reports (7–9). In brief, the forearm volume (i.e., from elbow to wrist) was assessed by water displacement before the instrumentation. The nondominant forearm was fitted with three occlusion cuffs from the wrist to the elbow. A fourth cuff was placed on the upper arm. From the wrist to the upper arm, the cuffs were inflated to 250 mmHg in sequence. Then the three cuffs on the forearm were deflated and removed, while the upper arm cuff remained inflated. After 4-min preinfusion, data were collected, and normal saline (0.9% concentration) equal to 5% arm volume (∼40–70 ml) was infused into the occluded forearm via an intravenous catheter in the antecubital fossa at a rate of 30 ml/min with a pump (∼80–140 s). After 5 min from the end of infusion, the upper arm cuff was deflated.

Data Analysis

Data were sampled at 200 Hz via a data acquisition system (MacLab, AD Instruments, Castle Hill, Australia). Mean arterial pressure (MAP) was calculated from the Finometer waveform during each trial, while the baseline MAP was corrected by an automated sphygmomanometer from an upper arm. As described in our previous reports (6), MSNA bursts were first identified in real time by visual inspection of the data, coupled with the burst sound from the audio amplifier. These bursts were further evaluated by a computer program that identified bursts based upon fixed criteria, including an appropriate latency following the R-wave of the electrocardiogram (6). Integrated MSNA was normalized by assigning a value of 100 to the mean amplitude of the top 10% largest bursts during the first 5-min baseline period before any intervention for each visit (6). Normalization of the MSNA signal was performed to reduce variability between recordings attributed to factors, including needle placement and signal amplification (16) and would not affect the relative changes between the baseline and the intervention. Total MSNA activity was calculated from burst area of the integrated neurogram on a beat-by-beat basis.

O&S and occlusion-alone trials.

The average values of MSNA, HR, and MAP over the 5-min baseline, the first minute (Min 1), and the second minute (Min 2) of O&S or occlusion alone were used in the statistical analyses. The changes from the baseline to Min 2 were used as the responses for O&S or occlusion alone.

Volume infusion trial.

Because the peak MSNA and MAP responses occurred toward the end of the infusion period (7–10), the mean values obtained during the last 30 s of infusion and the first 30 s of the postinfusion period (i.e., the entire 60 s) were defined as the “Maximal responses”. The average values for MSNA, MAP, and HR were analyzed over the 5 min of freely perfused baseline, forearm occlusion, the last 3 min of the preinfusion, and the “Maximal responses”. The changes (delta) from the preinfusion to the maximal response were used as the responses.

Statistics

Statistical analyses were performed with the use of SigmaStat software (SPSS Science). The absolute values of cardiovascular variables and MSNA in the trials of arm O&S and the occlusion alone on the arm were used to examine the effects of the stages of the interventions in the protocol (i.e., baseline, Min 1, and Min 2) and the type of the interventions (O&S vs. occlusion alone) via repeated-measures two-way ANOVA. When appropriate, Tukey post hoc analyses were employed. The response (i.e., the change from the baseline to Min 2) to arm O&S and the response to occlusion alone on the arm were compared with paired t-tests. When the normality test failed, Wilcoxon signed rank tests were employed. In a similar manner, the cardiovascular variables and MSNA in the leg O&S and occlusion alone on the leg were compared. Moreover, the relationships between the MSNA and cardiovascular responses to arm O&S and the responses to the leg O&S were analyzed via Pearson Product Moment Correlation analysis. The absolute values of MAP, HR, and MSNA over the stages during the volume infusion trials were used to examine the effects of the interventions in the protocol via repeated-measures one-way ANOVA. When appropriate, Tukey post hoc analyses were employed. The relationships between the MSNA and cardiovascular responses to arm O&S and the responses to the volume infusion were analyzed via Pearson Product Moment Correlation analysis. All values are reported as means ± SE. P values of <0.05 were considered statistically significant.

RESULTS

MSNA, MAP and HR responses to O&S

Representative tracings of calf circumference, HR, MSNA, and BP during leg O&S and occlusion alone are shown in Fig. 1. The O&S induced an increase in limb circumference that was significantly greater than seen during occlusion alone (Table 1). Skin blood flow in treated limbs decreased significantly during O&S or occlusion alone conditions (Table 1). Although the flowmetry reading was not zero, the pulse wave, which was seen in the skin blood flow traces in baseline, was eliminated during O&S or the occlusion-alone condition. The skin blood flow in the contralateral limb was not altered.

Fig. 1.

Representative tracing of calf circumference (Cir), heart rate (HR), integrated muscle sympathetic nerve activity (MSNA), and blood pressure (BP) during 100-mmHg negative pressure to an occluded leg (top), and occlusion alone of the leg (bottom). bpm, beats/min.

Table 1.

Hemodynamic and MSNA responses to O&S or occlusion alone

	Arm		Leg
	O&S	Occlusion	O&S	Occlusion
ΔCir %	1.3 ± 0.2*	0.4 ± 0.1	0.9 ± 0.2*	0.2 ± 0.1
ΔMAP, mmHg	4.3 ± 0.7*	1.3 ± 0.7	9.4 ± 1.4*	4.0 ± 1.0
ΔHR, beats/min	−2.6 ± 0.6	−1.3 ± 1.4	2.7 ± 1.5	−0.6 ± 1.2
ΔMSNA, bursts/min	6.7 ± 0.7*	1.9 ± 1.2	6.8 ± 0.7*	0.4 ± 1.3
ΔMSNA, bursts/100 beats	12.3 ± 1.6*	1.4 ± 2.0	8.2 ± 1.3*	0.7 ± 2.2
ΔMSNA, units/min	199 ± 14*	47 ± 27	172 ± 22*	33 ± 30
Treated ΔSkBF, %	−77.0 ± 2.8	−79.8 ± 3.1	−69.1 ± 5.1	−69.3 ± 5.1
Control ΔSkBF, %	−1.9 ± 2.4	−2.0 ± 3.2	5.8 ± 4.8	5.7 ± 4.6

Cir, limb circumference; MAP, mean arterial pressure; HR, heart rate.

Skin blood flow (SkBF) in the treated limb or the contralateral (control) limb was normalized as a percentage of the baseline (100%). Muscle sympathetic nerve activity (MSNA) was reported as burst rate (bursts/min), burst incidence (bursts/100 beats) and the total activity (units/min). All data are the responses during the second minutes of occlusion and suction (O&S) or occlusion alone (i.e., Min2, baseline). n = 14 for Cir; n = 19 for other variables.

^*P < 0.005 vs. occlusion alone.

O&S of a leg or an arm increased MAP and MSNA (Fig. 2). During leg O&S, HR increased (Min 1), and then fell to the baseline during Min 2. During arm O&S, the HR did not change during Min 1 and was below the baseline during Min 2. Occlusion alone on either the leg or the arm did not significantly alter any of these variables (Fig. 2). When expressed as the change from the baseline (Table 1), the changes in MAP and MSNA seen during a leg or arm O&S were significantly greater than the values observed during limb occlusion. Changes in HR during O&S were not different from the values observed during occlusion alone. During the leg O&S, the MAP responses weakly correlated with the MSNA response (for ΔMAP vs. ΔMSNA burst rate; r = 0.662, P = 0.003; for ΔMAP vs. ΔMSNA total activity, r = 0.606, P = 0.008). MAP and MSNA responses during the leg O&S weakly correlated with MAP and MSNA responses seen during arm O&S (Fig. 3).

Fig. 2.

MAP, HR, MSNA burst rate (BR; bursts/min), burst incidence (BI; bursts/100 beats), and total activity (units/min) during negative pressure to an occluded limb (O&S) and occlusion alone. Left: occlusion and suction (O&S) on an arm (Arm O&S), and the occlusion alone on the arm (Arm Occlu). Right: O&S on a leg (Leg O&S) and the occlusion alone on the leg (Leg Occlu). B: baseline: M1, the first minute; M2, the second minute. n = 19. *P < 0.05 vs. baseline. #P < 0.05 vs. occlusion alone at the respective period.

Fig. 3.

Correlations between the hemodynamic and MSNA responses induced by arm O&S and leg O&S. The responses are the changes from the baseline to the values during the second minute of O&S. n = 19.

Comparison of Arm O&S to Volume Infusion

Venous saline infusion evoked significant increases in MAP (P < 0.001, one-way ANOVA) and MSNA (P < 0.001, for both burst rate and total activity), and did not significantly alter HR in the 13 subjects in this study. During the “Maximal response” period (i.e., the last 30 s of infusion + the first 30 s of the postinfusion period), MAP (83.9 ± 2.0 to 98.2 ± 3.3 mmHg, P < 0.001), MSNA burst rate (19.1 ± 1.8 to 34.3 ± 2.8 burts/min, P < 0.001), and MSNA total activity (418 ± 55 to 977 ± 118 units/min, P < 0.001) were significantly greater than those during the preinfusion period. The MSNA responses seen during arm O&S (i.e., the changes) weakly correlated with responses evoked by volume infusions into the forearm (i.e., the change from the preinfusion to the “Maximal response”) (Fig. 4).

Fig. 4.

Correlations between the hemodynamic and MSNA responses induced by arm O&S and the responses induced by the volume infusion into the forearm. The arm O&S responses are the changes from the baseline to the values during the second minute of O&S. The responses to the infusion are the changes from the preinfusion to the maximal response. n = 13.

DISCUSSION

The main findings of the present study are 1) suction of an occluded lower or upper limb induced significant increases in MSNA and MAP; 2) the magnitude of MSNA and MAP responses during arm O&S correlated with those during leg O&S; and 3) the magnitude of MSNA responses during arm O&S correlated with those during saline infusion into the occluded forearm.

When humans rise to a standing position, MAP remains unchanged or rises slightly (13). This ability to maintain BP has been ascribed to disengagement of cardiopulmonary (24) and arterial baroreceptors (26). However, other systems have also been suggested as contributing to this effect. Prior animal studies (21) showed that elevated venous pressure increased the afferent nerve activity emanating from nerves subserving the femoral saphenous veins. It was speculated that these nerves played a role during orthostatic stress (27). We speculate that venous distension in lower limbs contributes to the MSNA activation seen with standing. The present report for the first time suggests that this reflex system is present in the lower limbs of humans and may contribute to BP control during orthostatic stress.

The occlusion cuff was inflated to 250 mmHg ∼10 s prior to applying the suction. Moreover, the results of the laser-Doppler flowmetry (i.e., substantial reduction and the elimination of pulse waves) confirmed that the limb was arterially occluded. Thus, the limb circumference increase was not due to a fluid translocation into the occluded limb. We can only speculate on the potential mechanisms for the limb circumference increase. First, the radial pressure gradient by the suction might induce fluid movement from the center to the superficial tissues (e.g., vessels) of the limb. Second, the blood in the limb segment between the occlusion cuff and the tank (see methods) might move to the limb segment in the tank. Importantly, because no fluid shift was induced from the central circulation, the responses seen were not due to a secondary change in central venous pressure and the disengagement of cardiopulmonary afferents. The lack of effect of occlusion alone suggests that the responses seen were not due to pressure of the occlusion cuff. Thus, the observed MSNA and MAP responses should be linked with the increased pressure gradient across the limb and/or the tissue deformation.

Prior reports have shown that a substantial number of group III and IV fibers end directly within the adventitia of the small vessels, including arterioles and venules within muscles (1, 25, 29, 30). It is also interesting to note that some group III and group IV afferents with free nerve endings in the triceps surae muscle increase their discharge in response to both the infusion of vasodilatory agents and in response to venous occlusion (17, 18). Our previous reports (8, 9) have shown that venous distension due to saline infusion into an arterially occluded forearm evokes a reflex increase in MSNA. We speculate that the increased pressure gradient across the vessels and/or the tissue deformation induced by either increasing volume in the vessels or by external limb suction stimulates afferent endings near the vessels, and, in turn, evokes the sympathetic activation.

Since we speculate that the sympathetic responses seen during the limb O&S can be evoked, at least partially, via similar mechanisms for the responses seen with volume infusions into an occluded forearm, we compared the volume infusion and the O&S intervention in the same limbs. The correlation between the magnitude of MSNA responses during the arm O&S and the magnitude of the responses during the saline infusion showed that the individuals with larger responses to arm O&S had larger responses to the volume infusion into the forearm, and vice versa. These observations suggest that the limb O&S could evoke the venous distension reflex. Moreover, the similar MSNA responses were observed when the suction was applied on an upper limb or a lower limb, and the magnitude of MSNA responses during arm O&S correlated with those during leg O&S. These data suggest that the venous distension reflex is present in the lower limbs of humans.

We should acknowledge that these correlations were “weak.” Many nonspecific factors (e.g., the arousal responses) could also contribute to the autonomic and cardiovascular responses during the limb O&S or infusions. These nonspecific factors might not be at the exact same level for the two trials and, thus, could decrease the correlation. We should also note that the limb O&S or the occlusion alone might induce the extravasation of fluid from the vessels into tissues. Although the intervals between the trials were over 15 min, we could not exclude the possibility that extravasation of fluid from one intervention to the next might have influenced the response of subsequent interventions. This might contribute to the variability in the data. The variability in the data will decrease the correlations.

We did not apply the infusion model to lower limbs, because we were concerned regarding the total amount of volume that would be needed to evoke lower limb venous distension. Specifically, our prior report (8) suggests that with the infusion model, ∼5% of the limb volume would need to be infused. Because the volume of a lower leg is ∼3–4 liters, we estimate that 150 ml (or more) of volume will be necessary for applying the infusion model to the lower limbs. Thus, when the occlusion cuff on the thigh is released, a large volume of fluid would enter the central circulation within a few seconds. While this would likely not be well tolerated in most subjects, we did not want to perform such an intervention without proof of its safety.

Previous reports by Lott et al. (19, 20) showed that suction of an unoccluded upper or lower limb caused vasoconstriction in the treated limb. It was speculated that the increases in transmural pressure would evoke vasoconstriction, probably via both myogenic and sympathetic mechanisms. Because the suction on an unoccluded limb could induce fluid shift from central to the treated limb, the roles of the cardiopulmonary baroreceptors could not be excluded in those studies (19, 20). The present data show that the limb suction in the absence of baroreceptor unloading evokes increases in sympathetic outflow. Thus, the present findings are different from the previous reports by Lott et al. (19, 20).

Previous studies showed that when the leg circulation was arrested with a cuff on the thigh, another cuff applied on the calf muscles led to an increase in BP (3, 32). Of note, the BP responses seen during muscle compression were abolished by epidural anesthesia (32). It should be noted that the reflex described in these prior reports is thought to be due to engagement of mechanically sensitive muscle afferents that play a role in exercise pressor reflex (3, 32). By contrast, our findings are due to a radial pressure gradient. We speculate that this radial gradient may lead to venous distension and activate the venous distension reflex.

HR increased during the first minute of leg suction and then declined toward baseline. Arm suction led to a fall in HR during the second minute. No significant HR response was seen during the saline infusion studies. We speculate that the vascular distension reflex does not significantly affect HR. The HR response seen in the first minutes of leg O&S might be due to an arousal response.

Because the volume/mass of a leg is much larger than an arm, one might expect the response to be greater in the leg than in the arm. Thus, it was surprising to us that MSNA responses to arm O&S were not different from those to leg O&S. We can only speculate on potential mechanisms. It is reasonable that the afferents in the forearm and leg may have different densities and sensitivities to a variety of stimuli. For example, it is clear that greater cardiovascular responses are evoked during exercise with upper limb muscles than with lower limb muscles (4, 23). Further work will be needed to better understand this observation.

It should be noted that the magnitude of increase in both sympathetic activity and BP are markedly greater during infusion than during limb suction. We speculate that because no fluid was shifted into the treated limb during O&S, the deformation of the limb and the vessels of the limb was less than the distension induced by the venous infusion model (i.e., 5% of the limb volume).

Study limitations

The structure of the airtight pressure tank used in our studies precluded our utilization of ultrasound methods to visually document venous distension. However, the pressure gradients across the limb were increased by the suction. In the present studies, the pressure gradient across arteries should also be increased. The afferent nerve endings were also on and close to the small arteries and arterioles in muscles (1, 25, 29, 30). Thus, we cannot exclude the possibility that the afferent endings on and/or close to arteries and arterioles might be also activated and contribute to the observed responses.

In conclusion, the presented data show that suction on an occluded lower or upper limb increases MSNA and MAP. These responses could be evoked via stimulation of afferent endings on or near the vessel wall. The presented data suggest that this reflex system is present in the lower limbs of humans. We speculate that this response can contribute to the BP control seen during orthostatic challenge.

Perspectives and Significance

The results of this study provide evidence that venous distension reflex exists in the lower limb and is engaged in the absence of changes in baroreceptor input. Moreover, it should be noted that the leg O&S induced ∼0.9% increase in circumference at the mid-calf and an estimated increase in volume of ∼1.8%. This increase in leg volume was similar with the volume change seen previously with −32 to −40 mmHg of LBNP (22). Thus, calf vascular distension seen with leg O&S in the present study is comparable to those seen with orthostatic stress. Therefore, we speculate that venous distension reflex is engaged during orthostatic stress and does contribute to sympathetic control during this intervention.

GRANTS

This work was supported by the National Institutes of Health Grants P01 HL-096570.

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the authors.

AUTHOR CONTRIBUTIONS

Author contributions: J.C. conception and design of research; J.C., C.A.B., M.D.H., R.C.D., and M.D.M. performed experiments; J.C. and L.I.S. analyzed data; J.C. interpreted results of experiments; J.C. prepared figures; J.C. and L.I.S. drafted manuscript; J.C. and L.I.S. edited and revised manuscript; J.C., C.A.B., M.D.H., R.C.D., M.D.M., and L.I.S. approved final version of manuscript.