Biomedical subjects

S Iwase

Publications and source records attributed to S Iwase.

At least 37 records · Page 2Linked to original sources

PubMed2001

Effects of lower body positive pressure on muscle sympathetic nerve activity response [correction of respopnse] to head-up tilt.

The benefits of lower body positive pressure (LBPP) are generally accepted for clinical treatment in medical emergencies caused by massive bleeding to maintain the systemic blood pressure. They are also used by NASA post spaceflight for preventing orthostatic hypotension in the astronauts. However, controversy still exists concerning the mechanisms underlying LBPP benefits. The purpose of this study was to test the hypothesis that the baroreflex-mediated enhancement in sympathetic activity would be attenuated by LBPP during an orthostatic challenge in humans. Specifically, we studied 1) the sympathetic activity responses by the microneurographic technique, using direct intraneural measurement of muscle sympathetic nerve activity (MSNA); and 2) the contributions of preload and afterload to the chances in MSNA response during orthostasis on application of LBPP. To accomplish these issues, MSNA was recorded microneurographically along with noninvasive measurement of the cardiovascular variables in all the subjects during exposure to a 70 degrees HUT with 30-mm Hg LBPP.

Adult↗

PubMed2000

Skin sympathetic neuroeffector response is attenuated dose-dependently by systemic prostaglandin E1 injection in humans.

To clarify the effects of prostaglandin E1 (PGE1) on the vasoconstrictive responses, we compared the correlation between the amplitude of integrated skin sympathetic nerve activity (SSNA) and per cent reduction in skin blood flow (SBF) before and after the infusion of lipo PGE1 and placebo (bolus one-shot infusion, single blind study), and constant rate infusion of PGE1 (10 and 50 ng kg(-1) min(-1) by infusion pump, dose-dependency study) in ten healthy men. SSNA was recorded microneurographically from the median nerve simultaneously with SBF by laser Doppler flowmetry at the index fingertip. The measurement was conducted 30 min after injection of lipo PGE1 or placebo, and during the drip infusion of 10 and 50 ng kg(-1) min(-1) of PGE1 with maneuvers to enhance SSNA. The resting and activated skin blood flow were not significantly different between 10 ng lipo PGE1 and placebo administration, and between baseline and 10, 50 ng kg(-1) min(-1) of PGE1 injection. The vascular response, defined as the slope of regression line between logarithm of amplitude of integrated SSNA bursts and the reduction in SBF, was significantly suppressed by injection of lipo PGE1 as compared with that by placebo. It was also decreased dose-dependently by the constant rate infusion of PGE1 (10 and 50 ng kg(-1) min(-1)). We concluded that the intravenous injection of PGE1 attenuates vasoconstrictive responses to SSNA, and analysis of the relations between SSNA and vasoconstrictive response, i.e. the neuroeffector response, is suggested to be an important tool to assess the drug effect.

Action Potentials↗

PubMed2000

Phosphorylation of Bcl-2 protein by CDC2 kinase during G2/M phases and its role in cell cycle regulation.

Although it has been reported that Bcl-2 phosphorylation is associated with certain types of apoptosis, there is much controversy over the functional significance of and the kinases responsible for the phosphorylation. In this study, we examined whether Bcl-2 is phosphorylated by CDC2 kinase, a master regulator of G(2)/M transition in the eukaryotic cell cycle. When CDC2 was activated by okadaic acid in HL-60 cells, Bcl-2 phosphorylation was readily induced. The phosphorylation was correlated with the accumulation of cells in G(2)/M phases, but was not proportional to the level of apoptosis. Furthermore, we found that Bcl-2 was phosphorylated during G(2)/M phases of normal cell cycle. The ability of CDC2 to phosphorylate Bcl-2 was confirmed by in vitro kinase assay with a highly purified CDC2-cyclin B complex. Using synthetic peptides and mutant cell lines, we identified threonine 56, one of two consensus sites for CDC2 within the Bcl-2 sequence, as a residue phosphorylated by CDC2. Mutation at threonine 56 abrogated the cell cycle inhibitory effect of Bcl-2 without affecting anti-apoptotic function. These results suggest that two distinct functions of Bcl-2 (anti-apoptosis and cell cycle inhibition) are differentially regulated by post-translational mechanisms such as phosphorylation. CDC2-mediated phosphorylation of Bcl-2 may play some physiological roles in the negative regulatory events during mitosis.

Amino Acid Substitution↗

PubMed2000

Effects of three days of dry immersion on muscle sympathetic nerve activity and arterial blood pressure in humans.

The present study was performed to determine how sympathetic function is altered by simulated microgravity, dry immersion for 3 days, and to elucidate the mechanism of post-spaceflight orthostatic intolerance in humans. Six healthy men aged 21-36 years old participated in the study. Before and after the dry immersion, subjects performed head-up tilt (HUT) test to 30 degrees and 60 degrees (5 min each) with recordings of muscle sympathetic nerve activity (MSNA, by microneurography), electrocardiogram, and arterial blood pressure (Finapres). Resting MSNA was increased after dry immersion from 23.7+/-3.2 to 40.9+/-3.0 bursts/min (p<0.005) without significant changes in resting heart rate (HR). MSNA responsiveness to orthostasis showed no significant difference but HR response was significantly augmented after dry immersion (p<0. 005). A significant diastolic blood pressure fall at 5th min of 60 degrees HUT was observed in five orthostatic tolerant subjects despite enough MSNA discharge after dry immersion. A subject suffered from presyncope at 2 min after 60 degrees HUT. He showed gradual blood pressure fall 10 s after 60 degrees HUT with initially well-maintained MSNA response and then with a gradually attenuated MSNA, followed by a sudden MSNA withdrawal and abrupt blood pressure drop. In conclusion, dry immersion increased MSNA without changing MSNA response to orthostasis, and resting HR, while increasing the HR response to orthostasis. Analyses of MSNA and blood pressure changes in orthostatic tolerant subjects and a subject with presyncope suggested that not only insufficient vasoconstriction to sympathetic stimuli, but also a central mechanism to induce a sympathetic withdrawal might play a role in the development of orthostatic intolerance after microgravity exposure.

Adult↗

PubMed2000

Increased vasomotor sympathetic nerve activity and decreased plasma nitric oxide release after head-down bed rest in humans: disappearance of correlation between vasoconstrictor and vasodilator.

We hypothesized that the relationship between resting levels of sympathetic vasoconstrictor nerve traffic and dilator substance nitric oxide (NO) release is altered after exposure to microgravity, resulting in abnormal peripheral resistance. To examine the hypothesis, we assessed muscle sympathetic nerve activity (MSNA) (microneurography), an indicator of NO release (plasma nitrite/nitrate concentrations) and leg vascular resistance (venous occlusion plethysmography) in 20 healthy male volunteers before and after 14 days of 6 degrees head-down bed rest (HDBR), the ground-based analogue of microgravity. MSNA increased, while plasma nitrite/nitrate concentrations decreased after HDBR. A significant positive correlation observed between MSNA and plasma nitrite/nitrate concentrations before HDBR disappeared after HDBR. Leg vascular resistance increased after HDBR. In conclusion, an imbalance between sympathetic vasoconstrictor traffic and NO release might contribute to elevated peripheral vascular resistance following HDBR.

Adult↗

PubMed2000

Muscle sympathetic nerve activity during handgrip and post-handgrip muscle ischemia after exposure to simulated microgravity in humans.

To examine the effect of 6 degrees head-down bed rest (HDBR) on vasomotor sympathetic responses to isometric forearm exercise, 16 healthy male subjects aged 20-36 years performed voluntary isometric handgrip (HG) at 30% of maximal voluntary contraction until fatigue, followed by 2 min of post-handgrip muscle ischemia (PHGMI) with 250 mmHg of cuff inflation, before and after 14 days of HDBR. Time to fatigue and maximal voluntary HG force were not affected by HDBR. Pre-exercise baseline muscle sympathetic nerve activity (MSNA, measured by microneurography), heart rate (measured by electrocardiogram) and mean blood pressure (measured by Portapres) increased after HDBR. Increases in MSNA were similar during HG but significantly lower during PHGMI (P < 0.01) after HDBR. Responses of heart rate and mean blood pressure during HG and PHGMI were not affected by HDBR. These results suggest that the magnitude of muscle metaboreflex during isometric forearm exercise might be attenuated after 14 days of simulated microgravity.

Adult↗

PubMed2000

Lineage-specific regulation of cell cycle control gene expression during haematopoietic cell differentiation.

To maintain the fidelity and integrity of blood formation, the cell cycle is under strict regulation during haematopoietic cell differentiation. To elucidate the molecular mechanisms of cell cycle regulation during haematopoiesis, we examined cell cycle control gene expression during lineage-specific differentiation from CD34+ progenitor cells. Expression of cyclin-dependent kinases (cdks) and cyclins, except cdk4, was generally suppressed in CD34+ cells freshly isolated from the bone marrow of healthy volunteers. Among four major cdk inhibitors, p16 was expressed more highly in CD34+ cells than in CD34-negative bone marrow mononuclear cells, whereas the amounts of p21 and p27 transcripts increased in the CD34- population. The behaviour of cell cycle control genes during haematopoietic differentiation was classified into four patterns: (i) universal upregulation (cdc2, cdk2, cyclin A, cyclin B and p21); (ii) upregulation in specific lineages (cyclin D1, cyclin D3 and p15); (iii) no induction or stable expression (cdk4, cyclin D2, cyclin E and p27); and (iv) universal downregulation (p16). Lineage-specific changes included the sustained elevation of cdc2 and cyclin A during erythroid differentiation, cyclin D1 and p15 induction in myeloid lineage and selective upregulation of cyclin D3 in megakaryocytes. Blocking induction of cyclin D3 resulted in the inhibition of megakaryocytic differentiation. These results suggest that the expression of cell cycle control genes is distinctively regulated in a lineage-dependent manner, reflecting the cell cycle characteristics of each lineage. Some of these genes play an essential role in the process of differentiation itself.

Antigens, CD34↗

PubMed2000

Effects of aging on cardiovascular responses to gravity-related fluid shift in humans.

BACKGROUND: Fluid shift induced by postural change causes autonomic neural responses of the cardiovascular system that buffer blood pressure fluctuation. The aim of the study was to clarify the effects of aging on cardiovascular autonomic functions in response to gravity-related fluid shift that unloads or loads the baroreceptors in human subjects. METHODS: A chest electrocardiogram, blood pressure by Finapres, and stroke volume by impedance method were measured in healthy young men (23-31 years old) and healthy elderly men (74-80 years old) during supine rest, at 90 degrees head-up tilt and thermoneutral head-out water immersion. Spectral analysis was applied to the time series data of the R-R intervals (heart rate variability [HRV]) and systolic blood pressure (blood pressure variability [BPV]). The arterial baroreflex gain for heart rate was estimated using frequency transfer function analysis. RESULTS: The young subjects had stable blood pressure, despite the larger amount of fluid shift induced by both tilt and immersion, and had marked changes in HRV and BPV. The elderly subjects failed to maintain stable blood pressure during these perturbations, despite less fluid shift and no significant changes in HRV and BPV. The arterial baroreflex gain for heart rate was not changed in the elderly subjects, whereas the gain decreased with upright in the young subjects and showed an increasing tendency during immersion compared with upright posture. CONCLUSIONS: These findings suggest that the adaptivity of the autonomic nervous system to gravity-related fluid shift is reduced in elderly people, and this may cause blood pressure instability.

Adult↗

PubMed2000

The epitope detected by cytotoxic T lymphocytes against thymus leukemia (TL) antigen is TAP independent.

Thymus leukemia (TL) antigens belong to the family of MHC class Ib antigens. We have shown in our previous studies that they serve as transplantation antigens, and can be recognized by both TCR alpha beta and TCR gamma delta cytotoxic T lymphocytes (CTL) with TL but not H-2 restriction. Although TL are known to be expressed TAP independently, it is unclear whether peptide loading on TL molecules is necessary for the formation of CTL epitopes. In the present study, we first showed that TL expression is beta(2)-microglobulin (beta(2)m)-dependent but TAP1 independent by flow cytometric analysis of thymocytes from beta(2)m- or TAP1-deficient mice crossed with TL transgenic mice expressing Tla(a)-3-TL on their thymocytes. Subsequently, we investigated the epitope recognized by CTL derived from C3H mice immunized with skin from a transgenic mouse expressing T3(b)-TL ubiquitously. Bulk CTL lines against TL from primary mixed lymphocyte cultures showed comparable cytotoxicity against T3(b)-TL transfectants of TAP2-deficient murine RMA-S grown at 37 degrees C to that against those grown at 25 degrees C. Furthermore, TCR alpha beta and TCR gamma delta CTL clones against TL recognized TL expressed on T3(b)-TL transfectants of RMA-S and Drosophila melanogaster cells having broad defects in peptide loading of MHC, and lysed these target cells. These results together indicate that TL-specific CTL populations primarily recognize epitopes expressed TAP independently.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Comparison of anti-tumor responses against TL positive lymphoma induced by skin grafting and dendritic cell immunization.

When the skin of Tg.Con.3-1 transgenic mice expressing the TL (thymus leukemia) antigen in most tissues is grafted on syngeneic C3H mice, it is rejected, and a cytotoxic T cell (CTL) response against the TL antigen is induced. In this study, we first demonstrated that growth of TL positive lymphoma is suppressed in mice immunized by skin grafting. Immunization with bone marrow derived dendritic cells (DCs) from Tg.Con.3-1, was also found to be associated with an anti-tumor response, but less potent than skin grafting. Relative CTL precursor frequency with DC immunization was also approximately only one third that of skin grafting. The numbers of IFN-gamma producing cells in responder CD8 and CD4 T cell populations were higher with DC immunization than with skin grafting. However, DC immunization seems to induce non-specific immune responses, as re-stimulation with TL negative C3H spleen cells resulted in induction of almost half the number observed with TL positive cells. Thus, the actual number of IFN-gamma producing cells in specific responses to TL is not necessarily larger than with skin grafting immunization. The present results altogether suggest that DC immunization is capable of inducing an anti-tumor reaction, but also possibly unwanted immune responses. In vitro monitoring of specific and non-specific responses in the immune system, thus, is of particular importance for future development of cancer immunotherapy.

Animals↗

PubMed2000

Baroreflex control of muscle sympathetic nerve activity after 120 days of 6 degrees head-down bed rest.

To examine how long-lasting microgravity simulated by 6 degrees head-down bed rest (HDBR) induces changes in the baroreflex control of muscle sympathetic nerve activity (MSNA) at rest and changes in responses of MSNA to orthostasis, six healthy male volunteers (range 26-42 yr) participated in Valsalva maneuver and head-up tilt (HUT) tests before and after 120 days of HDBR. MSNA was measured directly using a microneurographic technique. After long-term HDBR, resting supine MSNA and heart rate were augmented. The baroreflex slopes for MSNA during Valsalva maneuver (in supine position) and during 60 degrees HUT test, determined by least-squares linear regression analysis, were significantly steeper after than before HDBR, whereas the baroreflex slopes for R-R interval were significantly flatter after HDBR. The increase in MSNA from supine to 60 degrees HUT was not different between before and after HDBR, but mean blood pressure decreased in 60 degrees HUT after HDBR. In conclusion, the baroreflex control of MSNA was augmented, whereas the same reflex control of R-R interval was attenuated after 120 days of HDBR.

Adult↗

PubMed2000

Head-down bed rest alters sympathetic and cardiovascular responses to mental stress.

Astronauts usually work under much mental stress. However, it is unclear how and whether or not an exposure to microgravity affects physiological response to mental stress in humans. To examine effects of microgravity on vasomotor sympathetic and peripheral vasodilator responses to mental stress, we performed 10 min of mental arithmetic (MA) before and after 14 days of 6 degrees head-down bed rest (HDBR), a ground-based simulation of spaceflight. Total muscle sympathetic nerve activity (MSNA, measured by microneurography) slightly increased during MA before HDBR, and this increase was augmented after HDBR. Calf blood flow (measured by venous occlusion plethysmography) increased and calf vascular resistance (calculated by dividing mean blood pressure by calf blood flow) decreased during MA before HDBR, but these responses were abolished after HDBR. Increases in heart rate and mean blood pressure during MA were not different between before and after HDBR. These findings suggest that HDBR augmented vasomotor sympathoexcitation but attenuated vasodilatation in the calf muscle in response to mental stress.

Adult↗

PubMed2000

Murine Delta homologue, mDelta1, expressed on feeder cells controls cellular differentiation.

The Delta/Serrate-Notch pathway is involved in intercellular signaling that controls cell fate during the development of invertebrates and vertebrates. Delta is a prototype of Notch ligands and has been studied extensively in Drosophila. In higher vertebrates, four Delta/Serrate homologues and four Notch homologues have been identified. Recent studies showed that the murine Delta homologue, mDelta1, is essential in early embryogenesis. The biological activity of mammalian Delta and its roles in cellular differentiation, however, have remained unclear. In this study, we first surveyed expression of mDelta1 in the adult mouse and found it to be present in a wide range of tissues. For testing biological activity of mDelta1, we expressed a mDelta1 full-length cDNA in L cells using a eukaryotic expression vector. Effects of mDelta1 on cellular differentiation were examined in two independent systems, featuring C2C12 myogenic differentiation and multipotent murine bone marrow cell differentiation. Inhibition of the former was observed with mDelta1 expression on L cells, associated with suppression of myogenin, a myogenic transcription factor. Expression of mDelta1 in conjunction with GM-CSF promoted differentiation of bone marrow cells to myeloid dendritic cells at the expense of other lineages. Although the effects of mDelta1 on two differentiation systems appeared opposing, as inhibition occurring in one and induction in the other, this can be understood by the unifying concept of generation of diverse cell types from equivalent progenitors. Thus, the present study provided evidence that mammalian Delta participates in intercellular signaling, determining the cell fate in a wide variety of tissues.

Animals↗

PubMed2000

Vasomotor sympathetic nerve activity in men during bed rest and on orthostasis after bed rest.

BACKGROUND: Alterations in autonomic function are commonly seen during and after spaceflight, and its ground-based analog, 6 degrees head-down bed rest (HDBR). They may include peripheral vascular regulation, but vasomotor sympathetic efferent nerve discharges to peripheral vasculatures have not been examined. The aim of our study was to examine changes in vasomotor sympathetic nerve activity during HDBR and under orthostasis after HDBR. METHODS: We performed 6 d of HDBR on six male subjects, and measured muscle sympathetic nerve activity (MSNA) together with plasma norepinephrine concentrations in the supine position before HDBR and in 6 degrees head-down position on the sixth day (HDBR6) of HDBR. We also measured MSNA in head-up tilt (HUT) test before and after HDBR. RESULTS: On HDBR6, MSNA burst rate was the same (17+/-4 bursts x min(-1)) as that in supine position before HDBR (15+/-2 bursts min(-1)), but plasma norepinephrine concentrations were decreased to 1.14+/-0.10 pmol x ml(-1) compared with the supine value before HDBR (1.56+/-0.20 pmol x ml(-1), p<0.05). After HDBR, supine MSNA burst rate significantly increased by 58% to 24+/-4 bursts x min(-1). MSNA increment in response to HUT was similar between before (34+/-3 bursts min(-1) x sin HUT(-1)) and after (40+/-6 bursts x min(-1) x sin HUT(-1)) HDBR. CONCLUSIONS: Our findings suggest that: a) the relationship between MSNA and plasma norepinephrine concentrations was altered on the sixth day during HDBR; b) the vasomotor sympathetic nerve activity was enhanced after HDBR; and c) the augmentation of vasomotor sympathetic outflow to muscles under orthostasis was preserved after HDBR.

Adult↗

PubMed2000

[Microgravity and autonomic nervous system].

How microgravity influences autonomic function is still under investigation. Microgravity induces neuro-vestibular alterations and body fluid shift, and these two changes cause "space motion sickness(SMS)" and cardiovascular deconditioning. "Space motion sickness" is a autonomic syndrome that exhibits nausea, vomiting, headache, anorexia, pallor etc., whose incidence in Space Shuttle mission reaches 67.1%. There are several hypotheses for SMS mechanism: 1) sensory conflict, 2) fluid shift, 3) otolith asymmetry, 4) space orientation readaptation, 5) otolith tilt-translation reinterpretation, and these hypotheses are considered to be combined together to cause SMS. After space flight, 64% of the astronauts suffer from orthostatic intolerance, which is defined as incompletion of 15 min of 70 degrees head-up tilt. Several causes for the deconditioning have been hypothesized, dehydration followed by fluid shift, altered gain for baroreflex sensitivity, decreased venous capacitance, etc. In our previous studies, we recorded muscle sympathetic nerve activity(MSNA) by microneurography under simulated and actual microgravity conditions. Parabolic flight, which induces 20 sec of actual microgravity, suppressed MSNA to 50%. Head-out water immersion suppressed MSNA to 20% while gradual recovery was observed during 3 hours of immersion. Dry immersion for 3 days revealed that MSNA was enhanced after simulated microgravity while the response to orthostasis was unchanged. Bed rest for 6, 14, and 120 days and Neurolab Project clarified the same tendency for longer duration of simulated microgravity. These alterations in MSNA might be attributed to the development of cardiovascular deconditioning after microgravity exposure.

Autonomic Nervous System↗

PubMed2000

[Disseminated MALT lymphoma associated with macroglobulinemia].

We report a case of disseminated MALT lymphoma with macroglobulinemia in an 80-year-old man who presented with a persistent fever. A radiograph of the chest showed infiltration of the left lung and pleural effusion of the right lung. The fluid contained numerous atypical lymphoid cells, which were positive for CD19, CD20, and HLA-DR, and negative for CD5 and CD10. Analysis of a pleural biopsy sample demonstrated no abnormality. A CT scan of the abdomen showed extensive thickening of the wall of the stomach adjacent to a peritoneal mass. Endoscopic examination disclosed antral ulceration. Histopathological examination of gastric samples revealed infiltration by centrocyte-like cells and lymphoepithelial lesions. Serum electrophoresis detected a macroglobulin peak at 34.5 g/l, and immunoelectrophoresis revealed an IgM kappa component. A bone marrow aspirate showed infiltration by the same lymphoid cells as those in the pleural fluid. A chromosome study of the lymphoid cells from both the bone marrow and pleural fluid showed a normal karyotype. The final diagnosis was MALT lymphoma involving the stomach, lungs and bone marrow. The patient did not consent to chemotherapy, and instead was given oral prednisolone. He died of respiratory distress one year and four months after diagnosis. Autopsy revealed wide dissemination of the tumor cells.

Aged↗

PubMed2000

Leg venous compliance in orthostatic intolerance before and after 14-day head-down bed rest.

To test the hypothesis that increased leg venous compliance (LVC) is one of the contributory factors to orthostatic intolerance (OI) after simulated microgravity, 28 healthy young males were exposed to a 14-day head-down bed rest, and LVC was measured by venous occlusion plethysmography. Orthostatic tolerance was evaluated by a 60 degree head-up tilt (HUT) for 15 min. Sixteen subjects suffered from OI after the bed rest. They were then divided into orthostatic tolerance (non-fainters, n=12) and intolerance (fainters, n=16) groups. We found that fainters had significantly larger LVC before bed rest (0.055 +/- 0.003 vs. 0.065 +/- 0.002 ml 100 ml-1 mm Hg-1, non-fainter vs. fainter; P < 0.05). After bed rest, LVC markedly increased in both groups. In all the subjects calf circumference was reduced on average by 4.7% and the percent change in LVC was negatively correlated with the percent change in calf circumference when all subjects' data were combined after bed rest (r = -0.42, P < 0.05). Our results did not support the hypothesis that increased LVC is the contributory factor to OI after a 14-day bed rest; however, the mechanisms behind the large LVC in the fainters before bed rest are unclear, and the initial LVC might be a predictive indicator for OI after microgravity exposure.

Adult↗

PubMed2000

Arm elevation enhances muscle sympathetic nerve activity during static exercise.

The purpose of the present study was to evaluate the effect of hypoperfusion to the static-exercised-muscle induced by arm elevation on muscle sympathetic nerve activity (MSNA) recorded from the right tibial nerve (n= 10) by microneurography. Subjects performed static handgrip exercises (SHG) at 30% of maximal voluntary contraction (MVC) for 2 min, followed by 2 min of posthandgrip muscle ischemia (PHGMI) at the heart level (control) and with the arm elevated (50 cm above heart level). Basal heart rate, mean blood pressure and MSNA responses expressed as burst rate (bursts/min) and total MSNA (%) were unaffected by the arm-position. Heart rate response during SHG was not influenced by the arm elevation, while mean blood pressure and MSNA responses were increased by it (P<0.05). MSNA responses were increased during the second minute of the SHG period (P<0.05) and the PHGMI period (P<0.05) in the elevated arm position. In conclusion, arm elevation increased MSNA responses to SHG and PHGMI, suggesting an increased magnitude of muscle metaboreflex.

Adrenergic Fibers↗