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PubMed1995

Effect of microgravity on forearm subcutaneous vascular resistance in humans.

To test the hypothesis that the subcutaneous vascular constrictor response to an orthostatic stress in humans is augmented after exposure to microgravity, the following experiment was performed. Four male astronauts underwent a standardized stepwise lower body negative pressure (LBNP) profile 5 mo before and between 24 and 40 h after completion of the 10-day Spacelab D2 mission (STS-55). Forearm subcutaneous blood flow was continuously measured during LBNP by the 133Xe washout technique, and forearm subcutaneous vascular resistance (FSVR) was estimated by dividing mean arterial pressure by forearm subcutaneous blood flow. Relative to the pre-LBNP level, FSVR increased to 169 +/- 42 (P < 0.05), 176 +/- 12 (P < 0.05) and 158 +/- 27% during postflight LBNP of -11 (20 min), -23 (5 min), and -30 (7.5 min) mmHg, respectively. During the same LBNP levels of the same durations preflight, FSVR increased to 121 +/- 11 (not significant), 139 +/- 12 (P < 0.05), and 135 +/- 13% (P < 0.05), respectively. Thus, FSVR increased more promptly and, in three of the four subjects, was more pronounced during postflight than during preflight LBNP. In conclusion, the FSVR response was more prompt and tended to be accentuated after 1-2 days after exposure to 10 days of microgravity and could act as a defense mechanism to alleviate decreased orthostatic tolerance.

Adult↗
PubMed1996

Endothelium-derived nitric oxide activity in forearm vessels of tennis players.

The aim of this study was to determine whether physical conditioning induced by a repetitive exercise stimulus would elicit changes in the response of forearm resistance vessels to an infusion of substances that modulate nitric oxide synthesis. Forearm blood flow responses to a 5-min ischemic stimulus and intrabrachial infusion of acetylcholine, sodium nitroprusside, and NG-monomethyl-L-arginine were examined in the preferred and nonpreferred limbs of eight habitual tennis players. Forearm volume, girth, and grip strength were significantly greater in the preferred limb, indicating a bilateral difference in physical condition. This was associated with an enhanced reactive hyperemic response in the preferred limb (53.5 +/- 9.4 vs. 38.8 +/- 4.7 ml.100 ml-1.min-1; P < 0.05). No differences between the limbs were evident in response to acetylcholine, sodium nitroprusside, or NG-monomethyl-L-arginine. These results suggest that exercise training enhances the peak vasodilator capacity of the vasculature without influencing basal or stimulated activity of the nitric oxide dilator system in vivo.

Acetylcholine↗
PubMed1996

Dependence of muscle VO2 on blood flow dynamics at onset of forearm exercise.

The hypothesis that the rate of increase in muscle O2 uptake (VO2mus) at the onset of exercise is influenced by muscle blood flow was tested during forearm exercise with the arm either above or below heart level to modify perfusion pressure. Ten young men exercised at a power of approximately 2.2 W, and five of these subjects also worked at 1.4 W. Blood flow to the forearm was calculated from the product of blood velocity and cross-sectional area obtained with Doppler techniques. Venous blood was sampled from a deep forearm vein to determine O2 extraction. The rate of increase in VO2mus and blood flow was assessed from the mean response time (MRT), which is the time to achieve approximately 63% increase from baseline to steady state. In the arm below heart position during the 2.2-W exercise, blood flow and VO2mus both increased, with a MRT of approximately 30 s. With the arm above the heart at this power, the MRTs for blood flow [79.8 +/- 15.7 (SE)s] and VO2mus (50.2 +/- 4.0 s) were both significantly slower. Consistent with these findings were the greater increases in venous plasma lactate concentration over resting valued in the above heart position (2.8 +/- 0.4 mmol/l) than in the below heart position (0.9 +/- mmol/l). At the lower power, both blood flow and VO2mus also increased more rapidly with the arm below compared with above the heart. These data support the hypothesis that changes in blood flow at the onset of exercise have a direct effect on oxidative metabolism through alterations in O2 transport.

Adult↗
PubMed1998

Forearm training reduces the exercise pressor reflex during ischemic rhythmic handgrip.

We examined the effects of unilateral, nondominant forearm training (4 wk) on blood pressure and forearm metabolites during ischemic and nonischemic rhythmic handgrip (30 1-s contractions/min at 25% maximal voluntary contraction). Contractions were performed by 10 subjects with the forearm enclosed in a pressurized Plexiglas tank to induce ischemic conditions. Training increased the endurance time in the nondominant arm by 102% (protocol 1). In protocol 2, tank pressure was increased in increments of 10 mmHg/min to +50 mmHg. Training raised the positive-pressure threshold necessary to engage the pressor response. In protocol 3, handgrip was performed at +50 mmHg and venous blood samples were analyzed. Training attenuated mean arterial pressure (109 +/- 5 and 98 +/- 4 mmHg pre- and posttraining, respectively, P < 0.01), venous lactate (2.9 +/- 0.4 and 1.8 +/- 0.3 mmol/l pre- and posttraining, respectively, P < 0.01), and the pH response (7.21 +/- 0.02 and 7.25 +/- 0.01, pre- and posttraining, respectively, P < 0.01). However, deep venous O2 saturation was unchanged. Training increased the positive-pressure threshold for metaboreceptor engagement, reduced metabolite concentrations, and reduced mean arterial pressure during ischemic exercise.

Adult↗
PubMed2005

Gly16 + Glu27 beta2-adrenoceptor polymorphisms cause increased forearm blood flow responses to mental stress and handgrip in humans.

We hypothesized that the muscle vasodilatation during mental stress and exercise would vary among humans who are polymorphic at alleles 16 and 27 of the beta(2)-adrenoceptors. From 216 preselected volunteers, we studied 64 healthy, middle-aged normotensive women selected to represent three genotypes: homozygous for the alleles Arg(16) and Gln(27) (Arg(16)/Gln(27), n = 34), Gly(16) and Gln(27) (Gly(16)/Gln(27), n = 20), and Gly(16) and Glu(27) (Gly(16)/Glu(27), n = 10). Forearm blood flow (plethysmography) and muscle sympathetic nerve activity (microneurography) were recorded during 3-min Stroop color-word test and 3-min handgrip isometric exercise (30% maximal voluntary contraction). Baseline muscle sympathetic nerve activity, forearm vascular conductance, mean blood pressure, and heart rate were not different among groups. During mental stress, the peak forearm vascular conductance responses were greater in Gly(16)/Glu(27) group than in Gly(16)/Gln(27) and Arg(16)/Gln(27) groups (1.79 +/- 0.66 vs. 0.70 +/- 0.11 and 0.58 +/- 0.12 units, P = 0.03). Similar results were found during exercise (0.80 +/- 0.25 vs. 0.28 +/- 0.08 and 0.31 +/- 0.08 units, P = 0.02). Further analysis in a subset of subjects showed that brachial intra-arterial propranolol infusion abolished the difference in vasodilatory response between Gly(16)/Glu(27) (n = 6) and Arg(16)/Gln(27) (n = 7) groups during mental stress (0.33 +/- 0.20 vs. 0.46 +/- 0.21 units, P = 0.50) and exercise (0.08 +/- 0.06 vs. 0.03 +/- 0.03 units, P = 0.21). Plasma epinephrine concentration in Arg(16)/Gln(27) and Gly(16)/Glu(27) groups was similar. In conclusion, women who are homozygous for Gly(16)/Glu(27) of the beta(2)-adrenoceptors have augmented muscle vasodilatory responsiveness to mental stress and exercise.

Blood Flow Velocity↗
PubMed2002

Effects of chronic sympathectomy on vascular function in the human forearm.

To determine whether endothelial function is altered by chronic surgical sympathectomy, we infused ACh, isoproterenol, nitroprusside (NTP), and the nitric oxide synthase inhibitor NG-mono-methyl-L-arginine (L-NMMA) into the brachial arteries of nine patients 5-64 mo after thoracic sympathectomy for hyperhidrosis. Age- and gender-matched controls were also studied. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Lower body negative pressure was used to assess reflex vasoconstrictor responses. Tyramine, which acts locally and causes norepinephrine release from sympathetic nerves, was also administered via the brachial artery. FBF at rest was 2.5 +/- 0.4 ml x dl-1 x min-1 in the patients and 2.5 +/- 0.3 ml x dl-1 x min-1 in the controls (P = 0.95). The normal vasoconstrictor responses to lower body negative pressure were abolished in the patients. By contrast, tyramine produced dose-dependent vasoconstriction in the patients that was identical to that of controls. The dose-response curves to ACh were similar in patients and controls, with maximum values of 19.3 +/- 4.4 vs. 25.5 +/- 2.8 ml x dl-1 x min-1, respectively. L-NMMA reduced baseline FBF similarly and reduced the maximal FBF response to ACh in both groups (patients 8.9 +/- 3.5 vs. controls 9.7 +/- 2.5 ml x dl-1 x min-1). The vasodilation to isoproterenol was similar and blunted to the same extent in both groups by L-NMMA. The responses to NTP in patients and controls were similar and not affected by L-NMMA. We conclude that, in humans, chronic surgical sympathectomy does not cause major disruptions in vascular function in the forearm. The normal vasoconstrictor responses to tyramine indicate that there were viable sympathetic nerves in the forearm that were not engaged by LBNP.

Adult↗
PubMed2004

Dynamic response characteristics of local muscle blood flow regulatory mechanisms in human forearm exercise.

We sought to understand the nature of control mechanisms involved in the adaptation of exercising muscle hyperemia. Seven subjects performed rhythmic dynamic forearm exercise under two exercise conditions: small step 1 [step increase from rest to 40% peak forearm vascular conductance (FVC), in ml.min(-1).100 mmHg-1] for 5 min followed by small step 2 (further increase to 80% peak FVC for 5 min), and large step (step increase from rest to 80% peak FVC for 5 min). FVC data were fit with a two- (small step 1) and three-component (small step 2, large step) exponential as appropriate. For the rapid phase I response, FVC dynamic response characteristics (time delay, time constant) were not affected by the magnitude of the work intensity increase when the transition began from rest, but were slower in the 40-80% transition. Rest-80% gain was greater than either rest-40% or 40-80% transitions but represented the same proportion of the phase I + phase II gain across all transitions (57 vs. 56 vs. 57%, respectively, P = 0.975). For the slower phase II response, dynamic response characteristics were not affected by the magnitude of the work intensity increase when initiated from rest. The time constant was not altered when the transition began from exercise vs. rest. We conclude that 1) dynamic response characteristics of exercise hyperemia control mechanisms are not affected by the magnitude of work rate increase when forearm exercise is initiated from rest, 2) phase I but not phase II dynamic response characteristics are sensitive to baseline exercise intensity, and 3) the mechanisms contributing to phase I result in the same relative response magnitude, regardless of the size of the step increase in exercise intensity or the baseline from which it is initiated.

Adaptation, Physiological↗
PubMed2002

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation.

The relative contribution of endothelial vasodilating factors to acetylcholine (ACh)-mediated vasodilation in the forearm cutaneous microcirculation is unclear. The aims of this study were to investigate the contributions of prostanoids and cutaneous C fibers to basal cutaneous blood flow (CuBF) and ACh-mediated vasodilation. ACh was iontophoresed into the forearm, and cutaneous perfusion was measured by laser-Doppler flowmetry. To inhibit the production of prostanoids, four doses of acetylsalicylic acid (ASA; 81, 648, 972, and 1,944 mg) were administered orally. Cutaneous nerve fibers were blocked with topical anesthesia. Cyclooxygenase inhibition did not change basal CuBF or endothelium-mediated vasodilation to ACh. In contrast, ASA (972 and 1,944 mg) significantly reduced the C-fiber-mediated axon reflex in a dose-dependent fashion. Blockade of C-fiber function significantly reduced axon reflex-mediated vasodilation but did not affect basal CuBF or endothelium-dependent vasodilation. The findings suggest that prostanoids do not contribute significantly to basal CuBF or endothelium-dependent vasodilation in the forearm microcirculation. In contrast, prostanoids are mediators of the ACh-provoked axon reflex.

Acetylcholine↗
PubMed2004

Evidence of a myogenic response in vasomotor control of forearm and palm cutaneous microcirculations.

Previous investigations of autoregulatory mechanisms in the control of skin blood flow suffer from the possibility of interfering effects of the autonomic nervous system. To address this question, in 11 subjects cutaneous vascular responses were measured during acute changes in perfusion pressure (using Valsalva maneuver; VM) before and after ganglionic blockade via systemic trimethaphan infusion. Cutaneous vascular conductance at baseline (CVC(base)) and during the last 5 s of the VM (CVC(VM)) were measured from forearm (nonglabrous) and palm (glabrous) skin. During the VM without ganglionic blockade, compared with CVC(base), CVC(VM) decreased significantly at the palm [0.79 +/- 0.17 to 0.55 +/- 0.17 arbitrary units (AU)/mmHg; P = 0.002] but was unchanged at the forearm (0.13 +/- 0.02 to 0.16 +/- 0.02 AU/mmHg; P = 0.50). After ganglionic blockade, VM induced pronounced decreases in perfusion pressure, which resulted in significant increases in CVC(VM) at both forearm (0.19 +/- 0.03 to 0.31 +/- 0.07 AU/mmHg; P = 0.008) and palm (1.84 +/- 0.29 to 2.76 +/- 0.63 AU/mmHg; P = 0.003) sites. These results suggest that, devoid of autonomic control, both glabrous and nonglabrous skin are capable of exhibiting vasomotor autoregulation during pronounced reductions in perfusion pressure.

Adult↗
PubMed2006

Changes in tissue water content measured with multiple-frequency bioimpedance and metabolism measured with 31P-MRS during progressive forearm exercise.

Multiple-frequency bioimpedance analysis (MFBIA) has been used to determine the cellular water composition in the human body. It is noninvasive and has demonstrated good correlations with other invasive measures of tissue water. However, the ability of this method to study transient changes in tissue water in specific muscle groups has not been explored. In this study, MFBIA was used to assess changes in forearm intracellular water (ICW), extracellular water (ECW), and total water (TW) in seven healthy volunteers during and after a progressive wrist flexion exercise protocol. In an identical trial, (31)P magnetic resonance spectroscopy ((31)P-MRS) was used to assess changes in intracellular pH and phosphocreatine (PCr). At the completion of exercise, forearm ICW increased 12.6% (SD 0.07, P = 0.003), TW increased 10.1% (SD 0.06, P = 0.005), and no significant changes were recorded for ECW. A significant correlation was found between the changes in intracellular pH and changes in ICW during exercise (r = -0.84, P = 0.018). With the use of regression analysis, average changes in P(i), PCr, and pH were found to predict changes in ICW (R(2) = 0.98, P = 0.005). In conclusion, MFBIA was sensitive enough to measure transient changes in the exercising forearm muscle. The changes seen were consistent with the hypothesis that intracellular acidification and PCr hydrolysis are important mediators of cellular osmolality and therefore may be responsible for the increased volume of water in the intracellular space that is often recorded after short-term high-intensity exercise.

Adult↗
PubMed2003

Cyclic h-reflex modulation in resting forearm related to contractions of foot movers, not to foot movement.

During rhythmic voluntary oscillations of the foot, the excitability of the H-reflex in the Flexor Carpi Radialis (FCR) muscle of the resting prone forearm increases during the foot plantar-flexion and decreases during dorsiflexion. It is known that, when the two extremities are moved together, isodirectional (in-phase) coupling is the preferred form of movement association. Thus the above pattern of the H-reflex excitability modulation may favor the preferred coupling between the two limbs. To gain some clues about its origin, FCR H-reflex excitability was tested before and after modifying the phase relations between the activation [electromyogram (EMG)] of foot movers and foot movement, either by loading of the foot or by changing the movement frequency. After foot loading, the movement cycle was consistently delayed with respect to the onset of the EMG in Soleus (Sol) or Tibialis Anterior (TA) muscles. Simultaneously, the FCR H-reflex modulation advanced by that same amount with respect to the foot movement, thus remaining phase-locked to the EMG onsets. Similarly, when movement frequency was varied step-wise between 1.0 and 2.0 Hz, the foot movement was progressively delayed with respect to both the EMG onset (Sol and TA) and the FCR H-reflex modulation, so that the phase relation between the motor command to the foot and the H-modulation in the forearm remained constant. These results suggest that modulation of H-reflex in the forearm is tied to leg muscle contraction, rather than to foot kinematics, and point to a central, rather than kinesthetic, origin for the modulation.

Biomechanical Phenomena↗
PubMed1984

Cerebellar cortical activity during antagonist cocontraction and reciprocal inhibition of forearm muscles.

Monkeys were trained to perform a maintained isometric grip of the thumb and forefinger that elicited a simultaneous cocontraction of the antagonist muscles of the forearm. The same monkeys were also trained to flex and extend the wrist against a stop with the fingers extended and to maintain an isometric wrist position for 1.0-1.5 s. During wrist movement, some of the synergist forearm muscles contracted during both flexion and extension. However, during the maintained isometric wrist position, the prime mover and synergist muscles were reciprocally active or silent. In the culmen-simplex region of the cerebellar cortex bordering on the primary fissure, 62% of the Purkinje cells that were identified by the climbing fiber discharge and that changed firing frequency decreased activity during maintained prehension. Almost all of these same Purkinje cells were reciprocally active during isometric wrist flexion and extension, although three neurons had similar discharge patterns during movements in both directions. In contrast, 79% of the unidentified neurons recorded from the same region of the cerebellar cortex increased discharge frequency during prehension. In general, most of these same neurons had reciprocal patterns of discharge during wrist movement even though a few cells were active during the dynamic phase in both directions. Together, the Purkinje cells and the unidentified neurons with bidirectional response patterns were thought to be related to muscles active during both flexion and extension wrist movements. No cells were found that increased discharge with the static isometric wrist torque exerted in both directions. The discharge frequency of some Purkinje and some unidentified neurons could be shown to be related to prehensile force as well as wrist movement velocity and isometric wrist torque. These data suggest that the discharge of about two-thirds of the Purkinje cells related to forearm muscles located along the borders of the primary fissure may depend on whether antagonist muscles are activated reciprocally or coactively. As a consequence, these cells may play a role in the selection or alternation between either of these two modes of muscular contraction. The increased discharge of the remaining one-third of the Purkinje cells excited during antagonist coactivation may provide inhibition of nuclear cells to stabilize the posture at joints other than the wrist and fingers or, alternatively, they may act to reduce nuclear cell discharge in proportion to the intensity of cutaneous stimulation.

Animals↗
PubMed2000

Prosthetic graft placement using the deep forearm veins in hemodialysis patients: a preliminary report.

When the superficial arm veins are not suitable for the creation of a conventional endogenous arteriovenous (A-V) fistula or the placement of a prosthetic graft in the forearm, the use of the deep forearm veins as an outflow system to construct an A-V graft access seems to be a reasonable alternative. Using this approach, we placed 6 prosthetic grafts in 6 hemodialysis patients in whom conventional methods had failed. Adequate functioning of this 'deep vein'-type vascular access in these 6 patients has been maintained for 3, 6, 11, 15, 19 and 24 months, respectively, without complications or any need for further interventions. Only one graft failed after 6 months. Our preliminary results indicate that this technique can be used successfully when the superficial forearm veins have been exhausted, thus avoiding the use of upper-arm or axillary veins.

Adult↗
PubMed2003

Effect of local physical training on the forearm arteries and veins in patients with end-stage renal disease.

AIM: We investigate the effects of local training on the forearm vessels in patients with end-stage renal disease. METHODS: Fourteen hemodialysis patients were included. Handgrip training was performed for 8 weeks. The following parameters were measured at the beginning of the study and 4 and 8 weeks later: forearm circumference, maximal handgrip strength, and artery and vein parameters, including endothelium-dependent and endothelium-independent vasodilatation (using ultrasound and duplex Doppler scanning). RESULTS: The maximal handgrip strength increased significantly. The radial artery diameters were significantly higher after 8 weeks of training. The endothelium-dependent vasodilatation was found to be significantly increased after 4 and 8 weeks of training. The maximal vein diameters increased significantly with training, with preserved distensibility. CONCLUSIONS: The present study suggests that regular handgrip training increases the diameters of forearm vessels. It also improves endothelium-dependent vasodilatation. These changes point to the possible beneficial effects of daily handgrip training in chronic renal failure patients before arteriovenous fistula construction.

Adult↗
PubMed1990

Frictional properties of human forearm and vulvar skin: influence of age and correlation with transepidermal water loss and capacitance.

The dynamic friction coefficient between skin and a Teflon probe and its correlation with age, body weight, height, transepidermal water loss and skin capacitance was studied in vulvar and forearm skin of 44 healthy female volunteers. The friction coefficient of vulvar skin was 0.66 +/- 0.03 (mean +/- SEM) compared to that of forearm skin of 0.48 +/- 0.01. The difference was highly significant (p less than 0.001). Multiple-regression analysis showed that the vulvar skin friction coefficient was significantly correlated with capacitance as an indicator of stratum corneum hydration (p less than 0.01) but not with age, weight, height or transepidermal water loss. It is concluded that the high friction coefficient of vulvar skin may be due to the increased hydration of vulvar skin. Age-related differences seem to exist for transepidermal water loss and friction coefficient in forearm but not in vulvar skin.

Adult↗
PubMed2003

Hypercholesterolemia blunts forearm vasorelaxation and enhances the pressor response during acute systemic hypoxia.

OBJECTIVE: During hypoxia, active substances released by the endothelium play a key role in the cardiovascular and respiratory responses elicited to optimize oxygen delivery. As hypercholesterolemia is a major cause of endothelial dysfunction, it may interfere with these responses. METHODS AND RESULTS: We studied cardiovascular and ventilatory responses to acute systemic hypoxia in 14 patients with hypercholesterolemia (HC) and 13 control (CO) subjects. Oxygen saturation decreased similarly in both groups. Diastolic blood pressure increased only in the HC group (P=0.0002) and, despite systolic blood pressure increases both in the HC group, 140+/-4 (95% confidence interval [CI],131 to 149 mm Hg) to 154+/-4 mm Hg (95% CI,145 to 164 mm Hg), and in the CO group, 133+/-3 (95% CI,126 to 140 mm Hg) to 140+/-4 mm Hg (95% CI,132 to 148 mm Hg), the HC group showed an enhanced pressor response (P=0.03, group comparison). Both groups had increased forearm blood flow, but the decrease in forearm vascular resistance in the CO group, 40+/-5 (95% CI, 30 to 51 UR) to 31+/-4 UR (95% CI,23 to 39 UR) (P=0.0001) was not seen in the HC group, 29+/-3 (95% CI, 22 to 37 UR) to 26+/-3 UR (95% CI, 20 to 33 UR), (P=0.03, group comparison). CONCLUSIONS: Hypercholesterolemic patients demonstrate a hyperreactive pressor response and absence of forearm vasodilation during acute systemic hypoxia.

Acute Disease↗
PubMed2004

Block of inward rectifying K+ channels (KIR) inhibits bradykinin-induced vasodilatation in human forearm resistance vasculature.

OBJECTIVE: To investigate the possible involvement of inward rectifying K(+) channels (K(IR)) in the response of human resistance vessels to bradykinin in vivo. METHODS AND RESULTS: Drugs were administered via the brachial artery in healthy male volunteers and forearm blood flow was measured by venous occlusion plethysmography. Inhibition of K(IR) by barium chloride (4 micromol min(-1)) alone or with additional inhibition of Na(+)/K(+) ATPase (ouabain 2.7 micromol min(-1)) reduced responses to bradykinin (30 pmol min(-1)), by 26+/-8.3% and 36+/-7.2%, respectively (each P<0 0.05). Barium with ouabain plus inhibitors of prostaglandin (PG) and nitric oxide synthesis inhibited but did not abolish responses to bradykinin (51+/-2.8% inhibition; P<0.01); norepinephrine (240 pmol min(-1)) caused similar reduction of baseline blood flow, as did this combination of inhibitors, but did not significantly inhibit the response to bradykinin. Barium plus ouabain did not significantly reduce responses to acetylcholine or albuterol. CONCLUSIONS: A component of the vasodilator response to bradykinin in human forearm vasculature is mediated by K(IR). The possible involvement of inward-rectifying K+ channels (KIR) in the action of bradykinin was investigated by administering drugs via the brachial artery in healthy men. Barium selectively inhibited the forearm blood flow response to bradykinin, indicating that a component of this response is mediated by KIR.

Acetylcholine↗
PubMed1999

Exercise training increases basal nitric oxide production from the forearm in hypercholesterolemic patients.

The objective of this study was to investigate the effects of cycle training on basal nitric oxide (NO) production and endothelium-dependent dilator capacity in hypercholesterolemic patients in whom acetylcholine responsiveness is impaired. Nine sedentary hypercholesterolemic volunteers (total plasma cholesterol >6.0 mmol/L; 2 female) aged 44+/-3 years (mean+/-SEM) participated in the study. Subjects remained sedentary for 4 weeks and performed 4 weeks of home-based cycle training (3 x 30 minutes/week at 65% maximum oxygen consumption [VO(2)max]) in a randomized order. Arteriovenous nitrate/nitrite (NO(x)) gradient was assessed and plethysmography was used to measure the forearm blood flow responses to arterial infusions of acetylcholine, sodium nitroprusside, and N(G)mono methyl L-arginine. Training increased VO(2)max from 30.4+/-1.9 to 34.3+/-1.4 mL x kg(-1) x min(-1) (P=0.01). Intrabrachial diastolic blood pressure was reduced from 70+/-3 to 68+/-3 mm Hg (P=0.02) with training, whereas systolic pressure did not change. Plasma triglycerides and total, LDL, and HDL cholesterol were not different between interventions. In the sedentary state, there was a positive forearm arteriovenous difference in plasma NO(x) indicating net extraction (6.8+/-4.0 nmol x 100 mL(-1) x min(-1)), whereas in the trained state this difference was negative, indicating net production (-5.8+/-5.8 nmol x 100 mL(-1) x min(-1); P=0.03). N(G)mono methyl L-arginine, at a dose of 4 micromol/min, caused a greater vasoconstriction after training (79.6+/-3.4% versus 69.9+/-6.8%; P=0.05). Acetylcholine and sodium nitroprusside induced dose-dependent elevations in forearm blood flow that were unaffected by training. These data suggest that basal release of endothelium-derived NO is increased with 4 weeks of home based training in hypercholesterolemic patients, independently of lipid profile modification. This may contribute to the cardiovascular protective effects of exercise training, including reduced blood pressure.

Acetylcholine↗