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1 Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1; and 2 Department of Anesthesiology, Mayo Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905
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ABSTRACT |
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Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
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We tested the hypothesis that ACh or nitric oxide (NO) might be involved in the vasodilation that accompanies a single contraction of the forearm. Eight adults (3 women and 5 men) completed single 1-s-duration contractions of the forearm to raise and lower a weight equivalent to ~20% maximal voluntary contraction through a distance of 5 cm. In a second protocol, each subject had a cuff, placed completely about the forearm, inflated to 120 mmHg for a 1-s period, then released as a simulation of the mechanical effect of muscle contraction. Three conditions were studied, always in this order: 1) control, with intra-arterial infusion of saline; 2) after muscarinic blockade with atropine; and 3) after NO synthase inhibition with NG-monomethyl-L-arginine (L-NMMA) plus atropine. Forearm blood flow (FBF), measured by combined pulsed and echo Doppler ultrasound, was reduced at rest with L-NMMA-atropine compared with the other two conditions. After the single contraction, there were no effects of atropine, but L-NMMA reduced the peak FBF and the total postcontraction hyperemia. After the single cuff inflation, atropine had no effects, whereas L-NMMA caused changes similar to those seen after contraction, reducing the peak FBF and the total hyperemia. The observation that L-NMMA reduced FBF in response to both cuff inflation and a brief contraction indicates that NO from the vascular endothelium might modulate the basal level of vascular tone and the mechanical component of the hyperemia with exercise. It is unlikely that ACh and NO from the endothelium are involved in the dilator response to a single muscle contraction.
human forearm; exercise hyperemia; pulsed Doppler ultrasound; atropine; NG-monomethyl-L-arginine
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
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AFTER A SINGLE MUSCLE CONTRACTION, there is an increase in blood flow that is a consequence of both mechanical effects of the muscle pump that alter the perfusion pressure gradient across the capillary bed (23) and dilation of the resistance vessels (1, 4, 14). Recently, Tschakovsky et al. (26) observed that the increase in blood flow to the forearm (FBF) in response to a single, 1-s contraction was greater than the hyperemia that followed a single 1-s inflation-deflation of a cuff around the forearm. They concluded that a rapid vasodilation contributed to the greater flow observed with voluntary muscle contraction compared with the mechanical pumping of the cuff and that vasodilation was detectable within 2 s (26). The substance or mechanism responsible for this rapid dilation has not been resolved.
Anrep and von Saalfeld, in their 1935 paper (1), concluded that a stable vasodilator substance was released after a 0.15-s duration contraction in the dog gastrocnemius muscle and that the amount of dilator substance increased as the duration of the contraction increased. More recently, various authors have speculated on the potential vasodilator role of locally released autacoids, including acetylcholine (ACh) and nitric oxide (NO) (10, 15, 22). These endothelial cell-derived substances are believed to be released at basal levels and in response to increased shear stress within the arterial system (9, 13). There is, however, considerable controversy regarding the role of autacoids in exercise-induced vasodilation (8, 10). As an alternative to the theory of an endothelial source of ACh released from dog femoral arteries in response to increased flow rate (15), Segal and colleagues (see Refs. 21, 22, 27) have revived the hypothesis that ACh released at the neuromuscular junction might diffuse to nearby capillaries and, via a transmitted response, coordinate dilation of the arterioles. There is evidence that transmission via endothelial cell-to-cell communication is quite rapid (21, 25).
The purpose of this study was to examine the potential roles of ACh and NO in the immediate vasodilatory response to a single, short-duration, muscle contraction. These responses were compared with the change in blood flow immediately after release of a cuff that was inflated aroundthe forearm for a similar duration in an effort to simulate the mechanical effects of muscle contraction. To evaluate the contribution of ACh, atropine was infused into the brachial artery to block muscarinic receptors. This blockade was combined with inhibition of NO synthase by intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA) to further investigate the contribution of an ACh-independent NO effect.
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
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Subjects. Eight healthy subjects (3 women, 5 men) volunteered for this study. The mean age of the subjects was 25.4 ± 1.8 (SE) yr, height was 179.7 ± 1.9 cm, and weight was 76.0 ± 3.3 kg. Informed consent was obtained from the subjects, and approval of the protocol was acquired from the Institutional Human Subjects Committee of the Mayo Clinic in Rochester, MN, where the study was conducted.
Experimental design. Thirty minutes before testing, a 20-gauge, 4.5-cm Teflon arterial catheter (Arrow International, Reading, PA) was inserted into the brachial artery of the active arm. Aseptic techniques and local anesthesia (2 ml of 1% lidocaine) were used for this procedure. When the catheter was not being used for drug infusion, it was continuously flushed with 3 ml/h of saline with heparin (2 U/ml). The catheter was connected in series with a three-port connector: one port was for arterial pressure measurement, and the other two were for drug infusions from a mechanical syringe pump.
This study was completed as part of a larger study that investigated the roles of ACh and NO during rhythmic exercise (24). Each of the trials in the larger study required 5 min of exercise, during which a load of 4.4 kg (~10% of maximal voluntary contraction) was raised and lowered over 5 cm in a work-to-rest ratio of 1:2 s. To allow for adequate recovery from the previous exercise, ~20 min followed any of these tests before the single-contraction or cuff-inflation protocol began. For the single-contraction protocol, subjects were supine, with the arm positioned such that the forearm muscles were ~10 cm below the level of the heart. By squeezing a handgrip device connected to a pulley system, subjects lifted and lowered an 8.6-kg load (~20% maximal voluntary isometric contraction) through a vertical distance of 5 cm in 1 s. In the cuff-inflation and -deflation protocol, an inflatable cuff was placed around the forearm from the wrist to a point ~5 cm from the medial epicondyle of the humerus. The cuff was rapidly inflated to 120 mmHg, with the inflation-deflation cycle completed within 1 s to compress and empty the veins in an attempt to simulate the mechanical component of a muscle contraction. To minimize skin blood flow, a fan was directed at the arm. While the cuff was in place, but loosened during the contraction trials, a hose directed a flow of air under the cuff to minimize changes in skin blood flow. The laboratory room temperature was ~22°C. Testing order was the same for all subjects because of the long-lasting effects of the drugs, as described by Shoemaker et al. (24). During all drug infusions and during the Control saline infusion, the pump rate was always between 2 and 4 ml/min. To block the muscarinic receptors in the second condition, 0.2 mg of atropine (Gensia Pharmaceuticals, Irvine, CA) was infused in the last 3 min of a steady-state forearm exercise before the contraction and cuff-inflation trials. Drugs infused during exercise are more likely to affect blood vessels that will be open in subsequent exercise trials (7). ACh (IOLAB Pharmaceuticals, Claremont, CA) was infused at 16-32 µg/min for 3 min to test the efficacy of the muscarinic blockade. In the third condition, atropine was combined with L-NMMA (CalBiochem, La Jolla, CA) for the atropine + L-NMMA trial. L-NMMA was infused at 4 mg/min over 4 min of steady-state forearm exercise and 6 min of recovery, again to achieve distribution of this inhibitor to the vessels most likely to be open during the subsequent exercise trial. Supplemental atropine (0.05-0.1 mg) was given before the atropine + L-NMMA trial, and L-NMMA was infused at 2 mg/min for the duration of the trials. This dose of L-NMMA has been observed to be sufficient to reduce by at least 50% the vasodilation due to infusion of ACh, and it markedly blunts the vasodilator responses to physiological stimuli (5, 7).FBF. FBF was calculated beat by beat as the product of brachial artery mean blood velocity, measured with a 4-MHz pulsed Doppler ultrasound probe (model 500V, Multigon Industries, Mt. Vernon, NY), and the vessel cross-sectional area was measured with a 7.5-MHz linear probe that was operated in B mode (Toshiba model SSH-140A, Tochigi-Ken, Japan). The pulsed Doppler probe was fixed to the skin ~5 cm proximal to the elbow over the brachial artery. Probe position, sampling depth, and gate width were adjusted to optimize the insonation of the entire vessel. Processing of the Doppler shift spectra was completed with a Doppler signal processor as described previously (26).
Hyperemic responses.
The excess postcontraction and postinflation blood flow responses were
assessed from total hyperemia, expressed as the total flow above the
resting baseline value during the postcontraction or postinflation FBF
response. The peak change in FBF (peak 
FBF) was obtained as the peak
flow above baseline after release of the contraction or cuff inflation.
Statistics. Comparisons of the individual main effects of drug blockade were made with a two-way repeated measures analysis of variance. The level of significance was set at P < 0.05, and significant differences were analyzed further by using the Student-Newman-Keuls post hoc test. The data are expressed as means ± SE.
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RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
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ACh tests. In the Control condition, FBF increased above resting levels with administration of ACh by 128 ± 20 ml/min. Infusion of atropine reduced the magnitude of the blood flow increase in response to ACh by 71% to 36.9 ± 9.6 ml/min (P < 0.05).
Central hemodynamics. There were no effects of the drugs on central hemodynamics as evidenced by the similarity of the resting heart rates in the Control, atropine, and atropine + L-NMMA trials (62 ± 3, 55 ± 2, and 57 ± 3 beats/min, respectively). Resting mean arterial pressure was not affected by the drug infusions (95 ± 3, 95 ± 2, and 98 ± 2 mmHg in Control, atropine, and atropine + L-NMMA trials, respectively). Mean arterial pressure was not altered by a single contraction or by cuff inflation.
Resting FBF. Brachial artery diameter was 4.2 ± 0.2 mm at rest in each of the Control, atropine, and atropine + L-NMMA conditions (P > 0.05). Resting FBF before the contraction and the cuff inflation experiments was not different between Control and atropine treatments, but it was significantly reduced in the atropine + L-NMMA condition (P < 0.05, Fig. 1). This difference was entirely due to a significant reduction in mean blood flow velocity in the atropine + L-NMMA condition (P < 0.05; data not shown).
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Postcontraction blood flow.
The peak FBF observed after the 1-s voluntary muscle contraction in
the Control and atropine tests were significantly higher than those
observed in the atropine + L-NMMA tests (Table
1; P < 0.05). Changes in flow were exclusively due to changes in velocity,
because the diameter of the brachial artery was unchanged. The total
excess hyperemia above baseline observed with the single contractions
decreased relative to Control and atropine tests with atropine + L-NMMA (Fig. 1, Table 1;
P < 0.05).
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Blood flow after single cuff inflation.
As with the contraction, the peak FBF values immediately after
release of the cuff around the forearm in the Control and atropine
tests were greater than the values after the atropine + L-NMMA condition (Fig. 1, Table
1; P < 0.05). The total excess hyperemia above baseline after release of the cuff was also reduced from Control and atropine tests with atropine + L-NMMA (Fig. 1, Table
1; P < 0.05).
Postcontraction vs. postinflation.
The peak FBF and the total hyperemia were both greater after the
contraction than after the cuff inflation
(P < 0.05). The FBF remained above
the baseline flow values until the end of the 25-s observation period
in most tests after the single contraction, whereas FBF recovered to
baseline after the cuff inflation alone (Fig. 1).
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
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The major new findings of this study are that inhibition of NO synthase reduced the hyperemic responses to a brief mechanical stimulus and to a single muscle contraction. Peak blood flow in the atropine + L-NMMA condition was reduced by a similar magnitude to ~80% of that in the Control condition after the contraction and after the cuff inflation. This suggests that, after a single contraction, NO from the vascular endothelium played a role in modifying the mechanical factors that contribute to exercise hyperemia. It also suggests that a separate dilating mechanism that is not dependent on endothelial NO release is activated by a brief contraction. These observations extend and confirm our previous conclusions (26) that the hyperemia after a single contraction was due to both mechanical effects of the muscle pump and dilation of resistance vessels. Additionally, it appears that ACh release to luminal muscarinic receptors that were blocked by intra-arterial infusion of atropine did not play an obligatory role in the dilator responses to a single contraction.
In this study, we did not alter the order of drug administration, because atropine and L-NMMA each have long half-lives at the receptor sites. Therefore, their actions would have carried over into the next condition. Consequently, we decided to use the consistent order of atropine followed by L-NMMA. If we had used L-NMMA first, basal NO release as well as increased release as a consequence of ACh or increased shear rate, could not have been discriminated.
Over 60 years ago, Anrep and von Saalfeld (1) tested the hypothesis that ACh released from the neuromuscular junction might be involved in the vasodilation with exercise. They blocked muscular contraction with curare and then stimulated the motor nerve of the dog gastrocnemius muscle. No change in blood flow was observed, thus suggesting that ACh from the neuromuscular junction did not influence the vascular response. Similar observations were made recently in experiments with humans performing forearm contractions (6). Recently, Segal and colleagues (see Refs. 21, 22, 27) found evidence for diffusion of ACh from the neuromuscular junction to the vascular endothelium to induce vasodilation. Much recent interest has focused on the vascular endothelium as the source of vasodilator substances. ACh has been shown to be released from the endothelium (15) and to cause dilation by formation and release of NO (3, 15, 16). In addition, NO may be released in response to an increase in shear rate on the endothelial cells (13). Based on this hypothesis, the potential existed for ACh and NO to act rapidly on the resistance vessels to cause an active vasodilation that would contribute to the immediate hyperemia of exercise. Although these mechanisms might be operative in muscle preparations isolated from small animals, there was no evidence from our atropine experiments that ACh-mediated changes in vascular tone were important in the human forearm after a single muscle contraction. It must be recognized that intra-arterial infusion of atropine probably blocked the luminal muscarinic receptors, but we cannot be certain about blockade of abluminal receptors (20). The observation that intra-arterial infusion of atropine blocked the sweating response suggests that atropine might be widely distributed outside the blood vessels (19). Therefore, we cannot totally eliminate the possibility of stimulation of vasodilation by ACh from the neuromuscular junction as suggested by Segal and co-workers (see Refs. 21, 22, 27).
Inhibition of NO synthase activity by L-NMMA did cause a reduction in resting FBF. This observation is consistent with the findings of previous studies (5, 8, 10). There is some controversy regarding the role of NO in the hyperemia of exercise. Gilligan et al. (10) suggested that NO is involved in exercise-induced vasodilation of human forearm. In contrast, from studies of sustained isometric handgrip, Endo et al. (8) suggested that NO caused a reduction in flow but that this was simply a consequence of a general vasoconstriction at rest that carried over to exercise. Similar controversy exists from the study of animal muscle. For example, Hirai et al. (11) saw a role for NO in exercise hyperemia, especially in oxidative muscles of rats, whereas O'Leary et al. (18) concluded that NO was not important in determining hindlimb blood flow in running dogs. These experimental models differed from ours, not only in species, but also in systemic administration of drugs that caused elevated arterial pressure.
To test the relationship between resting and hyperemic flows, we have attempted to calculate a theoretical vascular conductance based on a series of assumptions as set out in the APPENDIX. The results of these calculations (see Table A1) support the notion that vascular conductance is reduced at rest and during the hyperemia by L-NMMA. Although the contraction experiments cannot completely eliminate the possibility of any NO contribution to the increase in vascular conductance, it is clear that any dilator substance did not overcome the effects of inhibition of NO synthesis to achieve the same absolute flow as in the heavy exercise studied in dogs by O'Leary et al. (18). It is evident that NO is involved in the normal exercise hyperemia. L-NMMA reduced the blood flow response to a single contraction and to repeated contractions (24). However, we believe that NO influences basal vascular tone and that the dilator response to exercise is superimposed on this tone. At least for the constant-load exercise intensities investigated in this previous research (24), the magnitude of the exercise hyperemia above baseline has been shown to be independent of NO. This conclusion is consistent with that of Klitzman et al. (12). These investigators noted that blood flow depended on the initial state of vascular tone and not necessarily the level of tissue oxygenation.
The possibility of a mechanically induced vasodilation has been suggested by the experiments on dog muscle by Mohrman and Sparks (17). However, recent investigations of the effects of repeated cuff inflation around human forearm muscle argue against this (26). When a cuff was repeatedly inflated for 1 s to 100 mmHg and then deflated for 2 s over 1 min, total blood flow increased through the forearm only when the arm was positioned below the heart. These results were explained by the increased pressure gradient across the muscle capillary bed that resulted from the mechanical emptying of the veins in a position with the arm below the heart. With the arm above the heart, gravity assisted in venous emptying so that the cuff did not modify the pressure gradient. There was no evidence of dilation due to the repeated compressions of the muscle.
Anrep and von Saalfeld (1) provided evidence for a vasodilator substance with a long half-life that appears to be released from contracting skeletal muscle. The long-lasting nature of the substance(s) makes it unlikely that these investigators were studying either ACh or NO. In agreement with this classic investigation of vasodilators involved in the immediate hyperemia with exercise, we suggest that the dilator(s) might be released from the active skeletal muscle. It is unknown whether NO might have been released from the skeletal muscle (2) but not blocked by intra-arterial L-NMMA. A mechanism that links blood flow to metabolic demand may be essential for efficient supply of oxygenated blood to the working muscle. Given the sensitivity of vascular endothelial cells to the local environment (21, 25), it is possible that very small changes in concentration of vasoactive substances such as potassium might be sufficient to evoke small early changes in vascular conductance. The mechanical effects of the muscle pump would be expected to increase flow in a manner that is dependent simply on the change in perfusion pressure across the working muscle and/or the mechanically stimulated local release of any dilating substances. In contrast, dilator mechanisms coupled to metabolism would be expected to increase flow in proportion to the metabolic demand.
In conclusion, this study has provided evidence that NO causes a reduction in blood flow and contributes to the mechanical component(s) of the hyperemic response seen after a brief contraction. It is also unlikely that ACh from endothelial sources plays a role in the contraction specific vasodilator response seen after a single muscle contraction. Finally, it appears that a dilating mechanism(s) not dependent on endothelial NO release is activated by a brief contraction. Future investigations will need to focus on the nature of this mechanism.
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APPENDIX |
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Top
Abstract
Introduction
Methods
Results
Discussion
Appendix
References
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Blood flow across a vascular bed is dependent on the pressure gradient and vascular conductance. Under resting conditions, it is possible to measure blood flow and arterial filling pressure but not effective venous pressure or vascular conductance. With our model of cuff inflation followed by deflation, we believe it is possible to assume that, immediately after release of the cuff pressure, the venous pressure must be close to zero, because blood has been displaced toward the heart. Thus it is possible to make a theoretical calculation of the pressure gradient and therefore vascular conductance in this time immediately after cuff release. First, we assumed that the mean arterial pressure was 100 mmHg, so that the arterial to venous pressure gradient was 100 mmHg immediately on release of the cuff. Next, we took the peak FBF and calculated a value for vascular conductance (Table A1). Under these assumptions, the vascular conductance was found to be similar for Control and atropine but less for atropine + L-NMMA immediately after cuff release.
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For the previous calculation to be valid, it was necessary to reason that vascular conductance was unchanged in response to a single cuff inflation followed by deflation. Although Mohrman and Sparks (17) suggested that myogenic vasodilation might take place, the experiments of Tschakovsky et al. (26) in which repeated cuff inflation/deflation failed to increase blood flow when the limb was placed above the heart argue against vasodilation in response to mechanical stimulus. Therefore, if vascular conductance was not affected by cuff inflation, then this value can be introduced in the calculation of the effective pressure gradient at rest (Table A1). The results of this calculation suggest that effective venous pressure was similar in all three test conditions.
Next, we applied the same assumption concerning venous pressure after a single muscle contraction. That is, venous pressure should be close to zero. From this, it can be appreciated that vascular conductance increased after contraction. Atropine + L-NMMA attenuated the increase in vascular conductance (Table A1).
The peak blood flow after cuff deflation in the atropine + L-NMMA tests was 78.3% of peak flow in the Control experiments. Similarly, after muscle contraction, peak flow in the atropine + L-NMMA tests was 80.9% of the Control. This similar reduction after cuff deflation or muscle contraction suggests that blood flow was not solely determined by metabolically derived vasodilators. Rather, appropriate nutritive flow is dependent on the interaction between metabolic demand, on one hand, and basal vascular tone and other mechanisms of enhanced oxygen availability, such as increased extraction, on the other (12).
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ACKNOWLEDGEMENTS |
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We are grateful to Lori Lawler, Maureen MacDonald, Heather Naylor, and Jorge Serrador for assistance with data collection.
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FOOTNOTES |
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This research was supported by a Natural Sciences and Engineering Research Council of Canada Grant (to R. L. Hughson) and by National Institutes of Health Grants HL-46493 (to M. J. Joyner) and RR-00585-24 (to the Mayo Foundation).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests: R. L. Hughson, Dept. of Kinesiology, University of Waterloo, Waterloo, ON, Canada N2L 3G1 (E-mail: hughson{at}cgsa.uwaterloo.ca).
Received 20 March 1998; accepted in final form 20 August 1998.
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  K. L. Jablonski, D. R. Seals, I. Eskurza, K. D. Monahan, and A. J. Donato High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men J Appl Physiol, November 1, 2007; 103(5): 1715 - 1721. [Abstract] [Full Text] [PDF]
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P. S. Clifford Skeletal muscle vasodilatation at the onset of exercise J. Physiol., September 15, 2007; 583(3): 825 - 833. [Abstract] [Full Text] [PDF]
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 A. J. Harper, L. F. Ferreira, B. J. Lutjemeier, D. K. Townsend, and T. J. Barstow Human femoral artery and estimated muscle capillary blood flow kinetics following the onset of exercise Exp Physiol, July 1, 2006; 91(4): 661 - 671. [Abstract] [Full Text] [PDF]
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 M. A. Vincent, L. H. Clerk, J. R. Lindner, W. J. Price, L. A. Jahn, H. Leong-Poi, and E. J. Barrett Mixed meal and light exercise each recruit muscle capillaries in healthy humans Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1191 - E1197. [Abstract] [Full Text] [PDF]
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D. J. Baker, D. J. Krause, R. A. Howlett, and R. T. Hepple Nitric oxide synthase inhibition reduces O2 cost of force development and spares high-energy phosphates following contractions in pump-perfused rat hindlimb muscles Exp Physiol, May 1, 2006; 91(3): 581 - 589. [Abstract] [Full Text] [PDF]
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P. S. Clifford, H. A. Kluess, J. J. Hamann, J. B. Buckwalter, and J. L. Jasperse Mechanical compression elicits vasodilatation in rat skeletal muscle feed arteries J. Physiol., April 15, 2006; 572(2): 561 - 567. [Abstract] [Full Text] [PDF]
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 J. W. G. E. VanTeeffelen and S. S. Segal Rapid dilation of arterioles with single contraction of hamster skeletal muscle Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H119 - H127. [Abstract] [Full Text] [PDF]
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D. Sheriff, P. S. Clifford, J. J. Hamann, Z. Valic, and J. B. Buckwalter Point: The muscle pump raises muscle blood flow during locomotion J Appl Physiol, July 1, 2005; 99(1): 371 - 375. [Full Text] [PDF]
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D. W. Wray, A. J Donato, A. Uberoi, J. P Merlone, and R. S Richardson Onset exercise hyperaemia in humans: partitioning the contributors J. Physiol., June 15, 2005; 565(3): 1053 - 1060. [Abstract] [Full Text] [PDF]
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N. R. Saunders, F. A. Dinenno, K. E. Pyke, A. M. Rogers, and M. E. Tschakovsky Impact of combined NO and PG blockade on rapid vasodilation in a forearm mild-to-moderate exercise transition in humans Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H214 - H220. [Abstract] [Full Text] [PDF]
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N. R. Saunders and M. E. Tschakovsky Evidence for a rapid vasodilatory contribution to immediate hyperemia in rest-to-mild and mild-to-moderate forearm exercise transitions in humans J Appl Physiol, September 1, 2004; 97(3): 1143 - 1151. [Abstract] [Full Text] [PDF]
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M. E. Tschakovsky and D. D. Sheriff Immediate exercise hyperemia: contributions of the muscle pump vs. rapid vasodilation J Appl Physiol, August 1, 2004; 97(2): 739 - 747. [Abstract] [Full Text] [PDF]
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D. S. DeLorey, S. S. Wang, and J. K. Shoemaker Evidence for sympatholysis at the onset of forearm exercise J Appl Physiol, August 1, 2002; 93(2): 555 - 560. [Abstract] [Full Text] [PDF]
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Z. Valic, J. S. Naik, S. B. Ruble, J. B. Buckwalter, and P. S. Clifford Elevation in resting blood flow attenuates exercise hyperemia J Appl Physiol, July 1, 2002; 93(1): 134 - 140. [Abstract] [Full Text] [PDF]
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L.-E. Chen, K. Liu, W.-N. Qi, E. Joneschild, X. Tan, A. V. Seaber, J. S. Stamler, and J. R. Urbaniak Role of nitric oxide in vasodilation in upstream muscle during intermittent pneumatic compression J Appl Physiol, February 1, 2002; 92(2): 559 - 566. [Abstract] [Full Text] [PDF]
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 D. J. Duncker, R. Stubenitsky, P. A.L. Tonino, and P. D. Verdouw Nitric oxide contributes to the regulation of vasomotor tone but does not modulate O2-consumption in exercising swine Cardiovasc Res, September 1, 2000; 47(4): 738 - 748. [Abstract] [Full Text] [PDF]
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J. S. Naik, Z. Valic, J. B. Buckwalter, and P. S. Clifford Rapid vasodilation in response to a brief tetanic muscle contraction J Appl Physiol, November 1, 1999; 87(5): 1741 - 1746. [Abstract] [Full Text] [PDF]
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), atropine (
), and atropine + NG-monomethyl-L-arginine
(L-NMMA; 
) conditions.
Compressive forces of muscle contraction and cuff inflation resulted in
transient retrograde blood flow. Peak increase in forearm blood flow
and total hyperemia to forearm after relaxation/deflation (at
time 0) were greater in Control and
atropine than in atropine + L-NMMA for both contraction and
cuff inflation (P < 0.05).