Obesity-induced skeletal muscle remodeling: A comparative analysis of exercise training and ACE-inhibitory drug in male mice.

Obesity over-activates the classical arm of the renin-angiotensin system (RAS), impairing skeletal muscle remodeling. We aimed to compare the effect of exercise training and enalapril, an angiotensin-converting enzyme inhibitor, on RAS modulation in the skeletal muscle of obese animals. Thus, we divided C57BL/6 mice into two groups: standard chow (SC) and high-fat (HF) diet for 16 weeks. At the eighth week, the HF-fed animals were divided into four subgroups-sedentary (HF), treated with enalapril (HF-E), exercise training protocol (HF-T), and combined interventions (HF-ET). After 8 weeks of treatment, we evaluated body mass and index (BMI), body composition, exercise capacity, muscle morphology, and skeletal muscle molecular markers. All interventions resulted in lower BMI and attenuation of overactivation in the classical arm, while favoring the B2R in the bradykinin receptors profile. This was associated with reduced apoptosis markers in obese skeletal muscles. The HF-T group showed an increase in muscle mass and expression of biosynthesis markers and a reduction in expression of degradation markers and muscle fiber atrophy due to obesity. These findings suggest that the combination intervention did not have a synergistic effect against obesity-induced muscle remodeling. Additionally, the use of enalapril impaired muscle's physiological adaptations to exercise training.

ER stress improvement by aerobic training or enalapril differently ameliorates pathological cardiac remodeling in obese mice.

Overactivation of the classic arm of the renin-angiotensin system (RAS) is one of the main mechanisms involved in obesity-related cardiac remodeling, and a possible relationship between RAS and ER stress in the cardiovascular system have been described. Thus, the aim of this study is to evaluate if activating the protective arm of the RAS by ACE inhibition or aerobic exercise training could overturn diet-induced pathological cardiac hypertrophy by attenuating ER stress. Male C57BL/6 mice were fed a control (SC) or a high-fat diet (HF) for 16 weeks. In the 8th week, HF-fed animals were randomly divided into HF, enalapril treatment (HF-En), and aerobic exercise training (HF-Ex) groups. Body mass (BM), food and energy intake, plasma analyzes, systolic blood pressure (SBP), physical conditioning, and plasma ACE and ACE2 activity were evaluated. Cardiac morphology, and protein expression of hypertrophy, cardiac metabolism, RAS, and ER stress markers were assessed. Data presented as mean ± standard deviation and analyzed by one-way ANOVA with Holm-Sidak post-hoc. HF group had increased BM and SBP, and developed pathological concentric cardiac hypertrophy, with overactivation of the classic arm of the RAS, and higher ER stress. Both interventions reverted the increase in BM, and SBP, and favored the protective arm of the RAS. Enalapril treatment improved pathological cardiac hypertrophy with partial reversal of the concentric pattern, and slightly attenuated cardiac ER stress. In contrast, aerobic exercise training induced physiological eccentric cardiac hypertrophy, and fully diminished ER stress.

Orthostatic intolerance: a handicap of aging or physical deconditioning?

Despite several studies that have been investigated physical inactivity and age-related effects on orthostatic tolerance, impaired hemodynamics and postural balance responses to orthostatic stress are incorrectly attributed to aging or sedentarism alone. The isolated effects from aging and sedentarism should be investigated through comparative studies between senior athletes and age-matched controls, and physical activity assessments on aging follow-up studies. On the other hand, bed rest and space flight studies mimic accelerated physical inactivity or disuse, which is not the same physiological decline provoked by aging alone. Thus, the elementary question is: could orthostatic intolerance be attributed to aging or physical inactivity? The main purpose of this review is to provide an overview of possible mechanisms underlying orthostatic tolerance contrasting the paradigm of aging and/or physical inactivity. The key points of this review are the following: (1) to counterpoint all relevant literature on physiological aspects of orthostatic tolerance; (2) to explore the mechanistic aspects underneath the cerebrovascular, cardiorespiratory, and postural determinants of orthostatic tolerance; and (3) examine non-pharmacological interventions with the potential to counterbalance the physical inactivity and aging effects. To date, the orthostatic intolerance cannot be attributed exclusively with aging since physical inactivity plays an important role in postural balance, neurovascular and cardiorespiratory responses to orthostatic stress. These physiological determinates should be interpreted within an integrative approach of orthostatic tolerance, that considers the interdependence between physiological systems in a closed-loop model. Based on this multisystem approach, acute and chronic countermeasures may combat aging and sedentarism effects on orthostatic tolerance.

Cardiovascular and Autonomic Responses after a Single Bout of Resistance Exercise in Men with Untreated Stage 2 Hypertension.

The aim of this paper is to assess the integrated responses of ambulatory blood pressure (BP), cardiac autonomic modulation, spontaneous baroreflex sensitivity (BRS), and vascular reactivity after a single bout of resistance exercise (RE) in men with stage 2 hypertension who have never been treated before. Ten hypertensive men were subjected to a RE session of three sets of 20 repetitions and an intensity of 40% of the 1-repetition maximum (RM) test in seven different exercises. For the control (CTR) session, the volunteers were positioned on the exercise machines but did not perform any exercise. Forearm blood flow was measured by venous occlusion plethysmography. We also analyzed the heart rate variability (HRV), ambulatory BP, blood pressure variability (BPV), and BRS. All measurements were performed at different timepoints: baseline, 20 min, 80 min, and 24 h after both RE and CTR sessions. There were no differences in ambulatory BP over the 24 h between the RE and CTR sessions. However, the area under the curve of diastolic BP decreased after the RE session. Heart rate (HR) and cardiac output increased for up to 80 and 20 min after RE, respectively. Similarly, forearm blood flow, conductance, and vascular reactivity increased 20 min after RE (p < 0.05). In contrast, HRV and BRS decreased immediately after exercise and remained lower for 20 min after RE. We conclude that a single bout of RE induced an increase in vascular reactivity and reduced the pressure load by attenuating AUC of DBP in hypertensive individuals who had never been treated with antihypertensive medications.

Inspiratory muscle training improves cerebrovascular and postural control responses during orthostatic stress in older women.

PURPOSE: We aimed to investigate the effect of inspiratory muscle training (IMT) on, hemodynamic, cerebrovascular and postural balance responses during orthostatic stress, in older women. METHODS: Fourteen elderly women were assigned to perform IMT at 50% of maximal inspiratory pressure (MIP) (IMT group, n = 8) or placebo training at 5% MIP (Sham group, n = 6), in a counter-balanced order, using an inspiratory threshold device for 4 weeks. During the protocol, MIP was tested weekly once. In a second visit, blood pressure, heart rate, stroke volume, cardiac output, middle cerebral artery blood flow velocity (MCAv), and ventilation parameters were recorded continuously at rest and during orthostatic stress testing, which was conducted on a force plate to measure center-of-pressure (COP) oscillations (postural balance) and the electromyographic activity of the right medial gastrocnemius and tibialis anterior. RESULTS: IMT increased MIP from second to 4th week. The drops in MCAv, stroke volume, and cardiac output, as well as COP displacements during initial orthostasis decreased post-IMT. CONCLUSION: IMT improves the interplay of the respiratory pump, hemodynamic, cerebrovascular and postural balance responses during orthostatic stress in older women.

Respiratory pump contributions in cerebrovascular and postural control responses during orthostatic stress in older women.

The acute inspiratory resistive load (IRL) may increase the respiratory pump contributes to hemodynamic responses during orthostatic stress. However, IRL effects on cerebrovascular and postural control interplay is unknown. Fourteen older women (65 ±â€¯4 years) performed two orthostatic tests with spontaneous breathing through acute experimental (-9 cm.H2O) or sham load impedance (0 cmH2O) connected to a pneumotachograph for breath-by-breath recordings on a facemask. Both tests were executed on a force plate, for postural balance analysis, and electromyographic activity records of calf muscles. Blood pressure, middle cerebral artery blood velocity (MCAv), heart rate (HR), stroke volume (SV), and cardiac output (CO) were continuously recorded. IRL reduced postural instability in the first five seconds at orthostatic position compared to sham. Although the mean blood pressure and MCAv were similar in both conditions, IRL reduced the SV and CO drops, and time to recover MCAv. Therefore, IRL improved postural control, CO and MCAv responses during initial orthostasis.

Effects of Heart Rate Reduction With Either Pyridostigmine or Ivabradine in Patients With Heart Failure: A Randomized, Double-Blind Study.

BACKGROUND: Heart rate (HR) reduction with ivabradine has been proved to reduce hospitalization and death from heart failure (HF). We sought to investigate whether pyridostigmine would effectively reduce HR in patients with chronic HF as compared with ivabradine. METHODS: Twenty-one patients with HF who were in sinus rhythm with a resting HR over 70 bpm, despite optimal medical treatment, were included in a randomized, double-blind study comparing pyridostigmine versus ivabradine. The initial dose of ivabradine was 5 mg twice daily to reach a target HR between 50 and 60 bpm and could be titrated to a maximum of 7.5 mg twice daily. Pyridostigmine was used in a fixed dose of 30 mg 3 times daily. RESULTS: The baseline HR for ivabradine and pyridostigmine groups was 89.1 (13.5) and 80.1 (7.2) bpm, respectively (P = .083). After 6 months of treatment, HR was significantly reduced to 64.8 (8.3) bpm in the ivabradine group (P = .0014) and 63.6 (5.9) bpm in the pyridostigmine group (P = .0001). The N-terminal pro-B-type natriuretic peptide was reduced in the ivabradine group (median: 1308.4 [interquartile range: 731-1896] vs 755.8 [134.5-1014] pg/mL; P = .027) and in the pyridostigmine group (132.8 [89.9-829] vs 100.7 [38-360] pg/mL; P = .002). Inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor were reduced in both groups. Exercise capacity was improved in both groups, with increments in volume of oxygen utilization (V˙O2; ivabradine: 13.1 vs 15.6, P = .048; pyridostigmine: 13.3 vs 16.7, P = .032). Heart rate recovery in the first minute postexercise was improved with pyridostigmine (11.8 [3.9] vs 18 [6.5]; P = .046), but not with ivabradine (13.3 [6.9] vs 14.1 [8.2]; P = .70). No differences in either group were observed in the myocardial scintigraphy with 123-iodine-metaiodobenzylguanidine. CONCLUSION: Both drugs significantly reduced HR, with improvements in exercise capacity and in neurohormonal and inflammatory profiles.

Effect of tamoxifen on fibrosis, collagen content and transforming growth factor-ß1, -ß2 and -ß3 expression in common bile duct anastomosis of pigs.

End-to-end anastomosis in the treatment for bile duct injury during laparoscopic cholecystectomy has been associated with stricture formation. The aim of this study was to experimentally investigate the effect of oral tamoxifen (tmx) treatment on fibrosis, collagen content and transforming growth factor-ß1, -ß2 and -ß3 expression in common bile duct anastomosis of pigs. Twenty-six pigs were divided into three groups [sham (n = 8), control (n = 9) and tmx (n = 9)]. The common bile ducts were transected and anastomosed in the control and tmx groups. Tmx (40 mg/day) was administered orally to the tmx group, and the animals were euthanized after 60 days. Fibrosis was analysed by Masson's trichrome staining. Picrosirius red was used to quantify the total collagen content and collagen type I/III ratio. mRNA expression of transforming growth factor (TGF)-ß1, -ß2 and -ß3 was quantified using real-time polymerase chain reaction (qRT-PCR). The control and study groups exhibited higher fibrosis than the sham group, and the study group showed lower fibrosis than the control group (P = 0.011). The control and tmx groups had higher total collagen content than the sham group (P = 0.003). The collagen type I/III ratio was higher in the control group than in the sham and tmx groups (P = 0.015). There were no significant differences in the mRNA expression of TGF-ß1, -ß2 and -ß3 among the groups (P > 0.05). Tmx decreased fibrosis and prevented the change in collagen type I/III ratio caused by the procedure.

Exercise training dose differentially alters muscle and heart capillary density and metabolic functions in an obese rat with metabolic syndrome.

NEW FINDINGS: What is the central question of this study? Regular exercise is recommended as a non-pharmacological approach for the prevention and treatment of metabolic syndrome. However, the impact of different combinations of intensity, duration and frequency of exercise on metabolic syndrome and microvascular density has not been reported. What is the main finding and its importance? We provide evidence on the impact of aerobic exercise dose on metabolic and microvascular alterations in an experimental model of metabolic syndrome induced by high-fat diet. We found that the exercise frequency and duration were the main factors affecting anthropometric and metabolic parameters and microvascular density in the skeletal muscle. Exercise intensity was related only to microvascular density in the heart. We evaluated the effect of the frequency, duration and intensity of exercise training on metabolic parameters and structural capillary density in obese rats with metabolic syndrome. Wistar-Kyoto rats were fed either a standard commercial diet (CON) or a high-fat diet (HFD). Animals that received the HFD were randomly separated into either a sedentary (SED) group or eight different exercise groups that varied according to the frequency, duration and intensity of training. After 12 weeks of aerobic exercise training, the body composition, aerobic capacity, haemodynamic variables, metabolic parameters and capillary density in the heart and skeletal muscle were evaluated. All the exercise training groups showed reduced resting systolic blood pressure and heart rate and normalized fasting glucose. The minimal amount of exercise (90 min per week) produced little effect on metabolic syndrome parameters. A moderate amount of exercise (150 min per week) was required to reduce body weight and improve capillary density. However, only the high amount of exercise (300 min per week) significantly reduced the amount of body fat depots. The three-way ANOVA showed a main effect of exercise frequency and duration for the improvement of metabolic syndrome and capillary density in skeletal muscle. Exercise intensity was a main factor in reversing microvascular rarefaction in the heart.

Adults with initial metabolic syndrome have altered muscle deoxygenation during incremental exercise.

OBJECTIVE: Reduced aerobic power is independently associated with metabolic syndrome (MetS) incidence and prevalence in adults. This study investigated whether muscle deoxygenation (proxy of microvascular O2 extraction) during incremental exercise is altered in MetS and associated with reduced oxygen consumption ( V˙O2peak ). METHODS: Twelve men with initial MetS (no overt diseases and medication-naive; mean ± SD, age 38 ± 7 years) and 12 healthy controls (HCs) (34 ± 7 years) completed an incremental cycling test to exhaustion, in which pulmonary ventilation and gas exchange (metabolic analyzer), as well as vastus lateralis deoxygenation (near infrared spectroscopy), were measured. RESULTS: Subjects with MetS, in contrast to HCs, showed lower V˙O2peak normalized to total lean mass, similar V˙O2 response to exercise, and earlier break point (BP) in muscle deoxygenation. Consequently, deoxygenation slope from BP to peak exercise was greater. Furthermore, absolute V˙O2peak was positively associated with BP in correlations adjusted for total lean mass. CONCLUSIONS: MetS, without overt diseases, altered kinetics of muscle deoxygenation during incremental exercise, particularly at high-intensity exercise. Therefore, the balance between utilization and delivery of O2 within skeletal muscle is impaired early in MetS natural history, which may contribute to the reduction in aerobic power.

Sex Differences in High Sensitivity C-Reactive Protein in Subjects with Risk Factors of Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is associated with a higher risk of all-cause mortality. High-sensitivity C-reactive protein (hsCRP) is a prototypic marker of inflammation usually increased in MetS. Women with MetS-related diseases present higher hsCRP levels than men with MetS-related diseases, suggesting sex differences in inflammatory markers. However, it is unclear whether serum hsCRP levels are already increased in men and/or women with MetS risk factors and without overt diseases or under pharmacological treatment. OBJECTIVE: To determine the impact of the number of MetS risk factors on serum hsCRP levels in women and men. Methods One hundred and eighteen subjects (70 men and 48 women; 36 ± 1 years) were divided into four groups according to the number of MetS risk factors: healthy group (CT; no risk factors), MetS ≤ 2, MetS = 3, and MetS ≥ 4. Blood was drawn after 12 hours of fasting for measurement of biochemical variables and hsCRP levels, which were determined by immunoturbidimetric assay. RESULTS: The groups with MetS risk factors presented higher serum hsCRP levels when compared with the CT group (p < 0.02). There were no differences in hsCRP levels among groups with MetS risk factors (p > 0.05). The best linear regression model to explain the association between MetS risk factors and hsCRP levels included waist circumference and HDL cholesterol (r = 0.40, p < 0.01). Women with MetS risk factors presented higher hsCRP levels when compared with men (p sex < 0.01). CONCLUSIONS: Despite the absence of overt diseases and pharmacological treatment, subjects with MetS risk factors already presented increased hsCRP levels, which were significantly higher in women than men at similar conditions.

Effect of continuous and interval aerobic exercise training on baroreflex sensitivity in heart failure.

INTRODUCTION: The ability of continuous aerobic exercise training (AET) to increase baroreflex control and cardiac function in heart failure (HF) has been well described, but the comparison between continuous and interval AET on these functions is inconclusive. OBJECTIVES: To compare the effects of continuous and interval AET on cardiac function and baroreflex sensitivity (BrS) in an experimental model of HF. METHODS: Rats were divided into the following groups: continuous training (HF-CT), intense interval training (HF-IIT), moderate interval training (HF-MIT), sedentary group (HF-SED), and sham sedentary (SHAM-SED). Animals underwent surgery to induce HF by ligation of the interventricular coronary artery. Six weeks after surgery, AET was started (8weeks, 3sessions/week). Echocardiography studies to assess cardiac function were performed before and after AET. At the end of the training protocols, the BrS index was assessed by stepwise intravenous infusions of sodium nitroprusside and phenylephrine. RESULTS: All methods of exercise prevented the HF-induced increase in left ventricular diameter in diastole observed in the HF-SED rats (0.88±0.09 vs. 1.03±0.09cm; P<0.05), but only the HF-CT (28.5±6.3 vs. 39.2±12.7%; P<0.05) and HF-MIT (31.0±8.5 vs. 42.0±10.3%; P<0.05) groups exhibited an increase in ejection fraction. Nevertheless, the HF-CT group was the only group that showed a tachycardia reflex higher than that of the HF-SED group (0.87±0.34 vs. 0.20±0.05bpm/mmHg; P<0.05) and similar to that of the SHAM-SED group (1.04±0.11bpm/mmHg). CONCLUSIONS: These results suggest that continuous and moderate interval training induced similar improvements in cardiac function but that only continuous training induced higher BrS in HF rats.

Effects of resistance exercise training on acyl-ghrelin and obestatin levels in hemodialysis patients.

BACKGROUND: Patients undergoing hemodialysis (HD) present altered levels of appetite hormones such as acyl-ghrelin (orexigenic) and obestatin (anorexigenic), which may contribute to anorexia. Physical exercise may affect these hormones and improve appetite in these patients. OBJECTIVES: The objective of this study is to evaluate the effects of a resistance exercise program in appetite hormones, body composition, and nutritional status in HD patients. DESIGN: Intervention study with the control group. SUBJECTS: Fifty-two patients on regular HD program were enrolled into two groups: 37 patients performed exercises (56.7% male, 45 ± 12.8 years, 57 (9-192) months on HD) and 15 patients comprised the control group (66.7% men, 50 ± 10.6 years, 57 (11-153) months on HD). MEASUREMENTS: Exercise program (performed with elastic bands and ankle cuffs in both lower limbs) was supervised three times a week during 6 months (72 sessions). Patients had their blood drawn in a regular HD day after overnight fasting, before and after 6 months of exercise program. Obestatin, acyl-ghrelin, routine biochemical parameters, quality of life, and anthropometric data were collected and analyzed before and after 6 months. RESULTS: After 6 months of exercise, obestatin levels reduced [from 3.0 ng/mL (2.3-3.4) to 1.9 ng/mL (0.6-3.4)] and acyl-ghrelin levels increased [from 21.5 pg/mL (1.3-77.7) to 37.2 pg/mL (16.7-94.1)] and the control group presented no significant differences in both plasma levels of hormones. Body composition and physical functional assessed by SF-36 and albumin levels (3.7 ± 0.3 to 3.9 ± 0.2, p < 0.05) improved after exercises. CONCLUSION: Six months of resistance exercises contributed to changes in plasma appetite hormones, body composition, and nutritional status in hemodialysis patients.

Is there association between uric acid and inflammation in hemodialysis patients?

BACKGROUND: Elevated serum uric acid has been associated with a variety of cardiovascular disease and with inflammation, but these have been little explored in chronic kidney disease (CKD). Elevated uric acid levels are common in CKD patients and could be involved in inflammatory milieu; our aim was to analyze the association between uric acid and inflammatory markers in hemodialysis (HD) patients. DESIGN: This was a cross-sectional study. SETTING: This study was conducted from private clinic, Rio de Janeiro, Brazil. PATIENTS: This study included 50 HD patients and 21 healthy subjects. METHODS AND PROCEDURES: This study included 50 HD patients [62% men, 54.3 ± 12.6 years, 57.5 ± 50.1 months on dialysis, and body mass index (BMI), 24.4 ± 4.1 kg/m2] and 21 healthy individuals (45% men, 50.7 ± 15.7 years and BMI, 25.5 ± 4 kg/m2). Uric acid was measured using uricase-PAP method; inflammatory [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP)] and atherosclerosis markers [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1)] were measured by a multiplexed assay. RESULTS: PATIENTS presented high levels of TNF-α, IL-6, CRP, VCAM-1, ICAM-1 (5.5 ± 2.1 pg/mL, 4.1 ± 1.6 pg/mL, 0.32 ± 0.30 mg/mL, 48.5 ± 8.5 ng/mL, 20.5 ± 15.9 ng/mL, respectively), compared with healthy individuals (2.4 ± 1.1 pg/mL, 2.7 ± 0.4 pg/mL, 0.11 ± 0.12 mg/mL, 23.8 ± 5.5 ng/mL, 7.2 ± 1.2 ng/mL, respectively) ( p < 0.04). Uric acid levels were also higher in HD patients (5.4 ± 1.3 mg/dL) than in healthy individuals (3.9 ± 0.9 mg/dL) ( p < 0.02). There was a positive correlation between uric acid and inflammatory markers, IL-6 (r = 0.30, p = 0.01), CRP (r = 0.37, p = 0.003), TNF-α (r = 0.40, p = 0.001), ICAM-1 (r = 0.53, p = 0.0001), and VCAM-1 (r = 0.45, p = 0.0001). CONCLUSION: These original data suggest that uric acid may have a role in inflammation and atherosclerosis in HD patients. However, further prospective studies involving intervention trials should be conducted in order to search for actual causality relationship between these markers.

ß-adrenergic receptor polymorphisms in susceptibility, response to treatment and prognosis in heart failure: implication of ethnicity.

Common functional polymorphisms in ß-adrenergic receptor (ßAR) genes have been associated with heart failure (HF) phenotypes and pharmacogenetic interactions with ßAR blockers. This study evaluated the association between ßAR polymorphisms and carvedilol drug response and prognosis in patients with HF. In this prospective cohort controlled study, 326 volunteers were enrolled [146 HF patients (ejection fraction (EF)<50% by Simpson) and 180 healthy controls]. Drug response was evaluated by echocardiography and outcomes were mortality and hospitalization. DNA was extracted from peripheral blood leukocytes, fragments were amplified by the polymerase reaction and genotyped by restriction fragment length polymorphism (RFLP) for Ser49Gly and Arg389Gly ßAR-1 polymorphisms and Gln27Glu and Arg16Gly ßAR-2 polymorphisms. The study population was in Hardy­Weinberg equilibrium. The survival rate was adjusted using the Kaplan-Meier method. HF patients showed the following characteristics: EF 35±9%, 69.9% male, age 59±13 years, 50.7% self-identified as black, 46% had ischemic etiology. The mean follow-up of 23 months showed 18 mortalities and 46 hospitalizations. The genotypes Glu27Glu (24.7 vs. 6.1%, p=0.0004) and Arg16Arg (72.6 vs. 22.8, p<0.0001) of ßAR2 polymorphisms and Gly49Gly (33.6 vs. 4.3%, p<0.0001) of the ßAR1 polymorphism were higher in HF patients compared with controls. Patients with hospital admission showed a significantly higher Gly389 allelic frequency (54.9 vs. 42.1%, p=0.039), and the trend prevailed among patients who succumbed to the disease (61.1%, p=0.047). Black patients with the Ser49Ser genotype showed a reduced survival compared with the Gly49Gly or Ser49Gly genotypes (p=0.028). There was no association between improved LVEF >20% and ßAR polymorphisms. HF patients with ß-blocker therapy and the Gly389 allele have reduced event-free survival compared to those carrying the Arg389 allele. Additionally, systolic HF outpatients undergoing ß-blocker therapy, self­identified as black and homozygous for Ser49Ser may have reduced event-free survival, while Glu27Glu, Arg16Arg and Gly49Gly genotypes may be associated with risk for HF.

Cerebrovascular responses to cold pressor test during static exercise in humans.

The purpose of this study was to determine whether exercise modulates the responses of middle cerebral artery blood velocity (MCA V(mean)) and cerebrovascular conductance to sympathetic stimulation (i.e. cold pressor test--CPT). To accomplish this, MCA V(mean) responses were assessed during CPT, static handgrip exercise (HG) at 30% of maximum voluntary contraction and combined condition (HG + CPT), assigned in a counterbalanced order, in eight healthy subjects. Blood pressure (BP), cardiac output (CO) and end-tidal partial pressure of carbon dioxide (PETCO(2)) were also measured non-invasively, and an index of vascular conductance was calculated for MCA (CVCi). BP increased from rest (P < 0·05) during CPT and HG and was additionally augmented during HG + CPT (P < 0·05 versus rest, CPT and HG). Despite the greater augmentation in BP during HG + CPT, MCA V(mean) was similarly increased during both HG (18·5 ± 2%, P < 0·05 versus rest) and combined condition (19·6 ± 2%, P < 0·05 versus rest). MCA V(mean) remained unchanged from rest during CPT only. CVCi was slightly reduced (P < 0·05) from rest during HG but was greatly reduced by CPT (P < 0·05 versus rest). The reduction in CVCi evoked by CPT at rest (-15 ± 2%, P < 0·05 versus rest) was significantly attenuated during HG (-8 ± 2%, P < 0·05 versus CPT). Increases in CO were similar in all trials, and PETCO(2) was unchanged from rest throughout the experiments. In summary, the cerebral conductance index decreases during the cold pressure test while that reduction is smaller when the CPT is conducted during the HG. This was critical for the maintenance of MCA V(mean) during combined condition.

Blood pressure and forearm blood flow after multiple sets of a resistive exercise for the lower limbs.

PURPOSE: Postexercise hypotension after resistive exercises has been described, but its underlying mechanisms are not well known. This study observed the blood pressure (BP) and vascular conductance after multiple sets of a lower-body resistive exercise. METHODS: BP and forearm blood flow (FBF; venous occlusion plethysmography) were assessed at rest and during reactive hyperemia, before and during postexercise recovery (10 and 60 min) in 16 men assigned to experimental (EG; n=9) and control (CG; n=7) groups. The EG performed the bilateral knee extension (10 sets of 15 repetitions with 90% of 15 repetitions maximum), whereas CG stayed at rest. RESULTS: No between-group differences were detected at rest in any of the variables (P>0.13). In EG, the systolic BP (mmHg) assessed 10 min after the exercise was significant compared with rest condition (104.4±1.5 vs. 111.3±2.0; P=0.011). The FBF (ml/100 ml/min/mmHg) and the forearm vascular conductance (FVC; ml/min/mmHg) in the postexercise recovery were lower than at rest in EG (FBF: rest=3.08±1.03, 10 min=2.21±0.68, P=0.007 and 60 min=2.33±0.47, P=0.018; FVC: rest=0.039±0.014, 10 min=0.029±0.008, P=0.02 and 60 min=0.030±0.006, P=0.03), but not in CG (FBF: resting=2.80±0.52, 10 min=2.87±0.53, P=0.22 and 60 min=2.97±0.73, P=0.14; FVC: resting=0.035±0.006, 10 min=0.029±0.010, P=0.32 and 60 min=0.029±0.013, P=0.13). No within-group (P=0.67) or between-group (P=0.11) changes were found in FBF and FVC during reactive hyperemia along postexercise recovery. CONCLUSION: Multiple sets of a single-resistance exercise induced postexercise hypotension and decreased FBF, albeit vasodilatation capacity was probably preserved.

Endothelial nitric oxide synthase polymorphisms and adaptation of parasympathetic modulation to exercise training.

PURPOSE: There is a large interindividual variation in the parasympathetic adaptation induced by aerobic exercise training, which may be partially attributed to genetic polymorphisms. Therefore, we investigated the association among three polymorphisms in the endothelial nitric oxide gene (-786T>C, 4b4a, and 894G>T), analyzed individually and as haplotypes, and the parasympathetic adaptation induced by exercise training. METHODS: Eighty healthy males, age 20-35 yr, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis, and haplotypes were inferred using the software PHASE 2.1. Autonomic modulation (i.e., HR variability and spontaneous baroreflex sensitivity) and peak oxygen consumption (VO(2peak)) were measured before and after training (running, moderate to severe intensity, three times per week, 60 min·day(-1), during 18 wk). RESULTS: Training increased VO(2peak) (P < 0.05) and decreased mean arterial pressure (P < 0.05) in the whole sample. Subjects with the -786C polymorphic allele had a significant reduction in baroreflex sensitivity after training (change: wild type (-786TT) = 2% ± 89% vs polymorphic (-786TC/CC) = -28% ± 60%, median ± quartile range, P = 0.03), and parasympathetic modulation was marginally reduced in subjects with the 894T polymorphic allele (change: wild type (894GG) = 8% ± 67% vs polymorphic (894GT/TT) = -18% ± 59%, median ± quartile range, P = 0.06). Furthermore, parasympathetic modulation percent change was different between the haplotypes containing wild-type alleles (-786T/4b/894G) and polymorphic alleles at positions -786 and 894 (-786C/4b/894T) (-6% ± 56% vs -41% ± 50%, median ± quartile range, P = 0.04). CONCLUSIONS: The polymorphic allele at position -786 and the haplotype containing polymorphic alleles at positions -786 and 894 in the endothelial nitric oxide gene were associated with decreased parasympathetic modulation after exercise training.