[Show abstract][Hide abstract] ABSTRACT: Functional sympatholysis is impaired in hypertensive animals and patients. Exercise training (ET) improves functional sympatholysis through a nitric oxide (NO)-dependent mechanism in normotensive rats. However, whether ET has similar physiological benefits in hypertension remains to be elucidated. Thus, we tested the hypothesis that the impairment in functional sympatholysis in hypertension is reversed by ET through a NO-dependent mechanism. In untrained normotensive Wistar-Kyoto rats (WKYUT; n = 13), untrained spontaneously hypertensive rats (SHRUT; n = 13) and exercise trained SHR (SHRET; n = 6), changes in femoral vascular conductance (FVC) were examined during lumbar sympathetic nerve stimulation (1, 2.5 and 5 Hz) at rest and during muscle contraction. The magnitude of functional sympatholysis (Δ%FVC = Δ%FVC muscle contraction - Δ%FVC rest) in SHRUT was significantly lower than WKYUT (1Hz: -2 ± 4 vs. 13 ± 3%; 2.5Hz: 9 ± 3 vs. 21 ± 3%; 5Hz: 12 ± 3 vs. 26 ± 3%, respectively, P<0.05). Three months of voluntary wheel running significantly increased maximal oxygen uptake in SHRET compared with non-trained SHRUT (78 ± 6 vs. 62 ± 4 ml kg(-1) min(-1), respectively, P<0.05) and restored the magnitude of functional sympatholysis in SHRET (1Hz: 9 ± 2%; 2.5Hz: 20 ± 4%; 5Hz: 34 ± 5%). Blockade of NO synthase (NOS) by L-NAME attenuated functional sympatholysis in WKYUT but not SHRUT. Furthermore, NOS inhibition significantly diminished the improvements in functional sympatholysis in SHRET. These data demonstrate that impairments in functional sympatholysis are normalized via a NO mechanism by voluntary wheel running in hypertensive rats.
[Show abstract][Hide abstract] ABSTRACT: Acute inflammation reduces flow-mediated vasodilation (FMD) and increases arterial stiffness in young healthy individuals. However, this response has not been studied in older adults. Therefore, the aim of this study was to evaluate the effect of acute induced systemic inflammation on endothelial function and wave reflection in older adults. Furthermore, an acute bout of moderate intensity aerobic exercise can be anti-inflammatory. Taken together, we tested the hypothesis that acute moderate intensity endurance exercise, immediately preceding induced inflammation, would be protective against the negative effects of acute systemic inflammation on vascular function. Fifty-nine healthy volunteers between 55 - 75 years of age were randomized in an exercise or control group. Both groups received a vaccine (induced inflammation) and sham (saline) injection in a counterbalanced crossover design. Inflammatory markers, endothelial function (FMD) and measures of wave reflection and arterial stiffness were evaluated at baseline, 24 hours and 48 hours after injections. There were no significant differences in endothelial function and arterial stiffness between the exercise and control group after induced inflammation. The groups were then analyzed together and we found significant differences in the inflammatory markers 24 and 48 hours post-acute inflammation compared to sham injection. However, FMD, augmentation index normalized for heart rate (AIx75) and β-stiffness did not change significantly. Our results suggest that acute inflammation induced by influenza vaccination did not affect endothelial function in older adults.
[Show abstract][Hide abstract] ABSTRACT: The most effective way of avoiding influenza is through influenza vaccination. However, the vaccine is ineffective in about 25% of the older population. Immunosenescence with advancing age results in inadequate protection from disease because of ineffective responses to vaccination. Recently, a number of strategies have been tested to improve the efficacy of a vaccine in older adults. An acute bout of moderate aerobic exercise may increase the efficacy of the vaccine in young individuals, but there is limited efficacy data in older adults who would benefit most.
This study sought to evaluate whether acute moderate intensity endurance exercise immediately prior to influenza vaccination would increase the efficacy of the vaccine.
Fifty-nine healthy volunteers between 55 - 75 years of age were randomly allocated to an exercise or control group. Antibody titers were measured at baseline prior to exercise and 4 weeks following vaccination. CRP and IL-6 were measured at 24 and 48 h post-vaccination.
Delta CRP and IL-6 at 24 and 48 h were significantly higher following vaccination as compared to the sham. There were no differences in the levels of antibody titers against the H3N2 influenza strain between groups. However, women in the exercise group had a significantly higher antibody response against the H1N1 influenza strain as compared to the men, probably due to lower pre vaccine titers. There were no significant differences in seroprotection between groups.
Acute moderate aerobic exercise was not immune-stimulatory in healthy older men, but may serve as a vaccine adjuvant in older women.
Medicine and science in sports and exercise 08/2013; 46(3). DOI:10.1249/MSS.0b013e3182a75ff2 · 3.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular disease is a leading cause of morbidity and mortality in patients post spinal cord injury (SCI). The prescription of exercise as a therapeutic modality for disease prevention in this population is promising. It is logical to suggest that the sooner an exercise program can begin the more benefit the patient will receive from the therapy. However, the time point after injury at which the requisite circulatory responses needed to support exercise are viable remains largely unknown. The skeletal muscle exercise pressor reflex (EPR) significantly contributes to cardiovascular control during exercise in healthy individuals. Experiments in patients with a chronic lateral hemi-section of the spinal cord (Brown-Séquard syndrome) suggest that the EPR, although blunted, is operational when examined months to years post injury. However, whether this critically important reflex remains functional immediately after lateral SCI or, in contrast, experiences a period of reduced capacity due to spinal shock has not been established. This study was designed to assess EPR function after acute lateral transection of the spinal cord. The EPR was selectively activated in seven decerebrate cats via electrically stimulated static contraction of the triceps surae muscles of each hindlimb before and after lateral hemi-section of the T(13)-L(2) region of the spinal cord. Compared to responses prior to injury, increases in mean arterial pressure (MAP) were significantly decreased when contracting the hindlimb either ipsilateral to the lesion (MAP = 17 ± 3 mmHg before and 9 ± 2 mmHg after) or contralateral to the lesion (MAP = 22 ± 5 mmHg before and 12 ± 4 mmHg after). The heart rate (HR) response to stimulation of the EPR was largely unaffected by induction of acute SCI. The findings suggest that the EPR maintains the ability to importantly contribute to cardiovascular regulation during exercise immediately following a Brown-Séquard-like injury.
Frontiers in Physiology 02/2013; 4:3. DOI:10.3389/fphys.2013.00003 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evidence suggests the muscle mechanoreflex, a circulatory reflex that raises blood pressure and heart rate (HR) upon activation of mechanically sensitive afferent fibers in skeletal muscle, is overactive in hypertension. However, the mechanisms underlying this abnormal reflex function have yet to be identified. Sensory input from the mechanoreflex is processed within the nucleus tractus solitarius (NTS) in the medulla oblongata. Within the NTS, the enzymatic activity of nitric oxide synthase (NOS) produces nitric oxide (NO). This centrally-derived NO has been shown to modulate muscle reflex activity and serves as a viable candidate for mediating the mechanoreflex dysfunction that develops in hypertension. We hypothesized that mechanoreflex dysfunction in hypertension is mediated by abnormal alterations in NO production in the NTS. Mechanically sensitive afferent fibers were stimulated by passively stretching hindlimb muscle before and after blocking the endogenous production of NO within the NTS via microdialysis of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 1 and 5 mM) in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Changes in HR and mean arterial pressure (MAP) in response to stretch were significantly larger in SHR compared to WKY prior to L-NAME dialysis. Attenuating NO production via L-NAME in normotensive rats recapitulated the exaggerated cardiovascular response to stretch observed in SHR. Dialyzing L-NAME in SHR further accentuated the increases in HR and MAP elicited by stretch. These findings support the contention that reductions in NO production within the NTS contribute to the generation of abnormal cardiovascular control by the skeletal muscle mechanoreflex in hypertension.
[Show abstract][Hide abstract] ABSTRACT: Mesoangioblasts are vessel-derived stem cells that differentiate into mesodermal derivatives. We have isolated postnatal aorta-derived mesoangioblasts (ADMs) that differentiate into smooth, skeletal, and cardiac muscle, and adipocytes, and regenerate damaged skeletal muscle in a murine model for Duchenne muscular dystrophy. We report that the marker profile of ADM is similar to that of mesoangioblasts isolated from embryonic dorsal aorta, postnatal bone marrow, and heart, but distinct from mesoangioblasts derived from skeletal muscle. We also demonstrate that ADM differentiate into myelinating glial cells. ADM localize to peripheral nerve bundles in regenerating muscles and exhibit morphology and marker expression of mature Schwann cells, and myelinate axons. In vitro, ADM spontaneously express markers of oligodendrocyte progenitors, including the chondroitin sulphate proteoglycan NG2, nestin, platelet-derived growth factor (PDGF) receptor α, the A2B5 antigen, thyroid hormone nuclear receptor α, and O4. Pharmacological inhibition of Rho kinase (ROCK) initiated process extension by ADM, and when combined with insulin-like growth factor 1, PDGF, and thyroid hormone, enhanced ADM expression of oligodendrocyte precursor markers and maturation into the oligodendrocyte lineage. ADM injected into the right lateral ventricle of the brain migrate to the corpus callosum, and cerebellar white matter, where they express components of myelin. Because ADM differentiate or mature into cell types of both mesodermal and ectodermal origin, they may be useful for treatment of a variety of degenerative diseases, or repair and regeneration of multiple cell types in severely damaged tissue.
Stem cells and development 07/2011; 21(7):1069-89. DOI:10.1089/scd.2011.0124 · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been shown that dendritic branching in neural cardiorespiratory and locomotor centers can be attenuated with exercise training (ET) initiated immediately after weaning. The purpose of this study was to determine whether neuroplastic changes occur within cardiorespiratory and locomotor centers due to ET after maturation. Male Sprague-Dawley rats (21 days old, n=28) were individually housed in standard cages. At 91 days of age, animals were divided into two groups: untrained (UN; n=14) and trained (TR; n=14). The TR group exercised spontaneously for 50 days on running wheels. ET indexes were obtained, including maximal O2 consumption, percent body fat, resting heart rate, and heart weight-to-body weight ratios. The brain was processed with a modified Golgi-Cox procedure. Impregnated neurons from the periaqueductal gray (PAG), posterior hypothalamic area (PH), nucleus of the tractus solitarius (NTS), cuneiform nucleus (CnF), rostral ventrolateral medulla, nucleus cuneatus, and cerebral cortex were examined. Neurons were traced and analyzed using the Sholl concentric ring analysis of dendritic branching. The mean total number of dendritic intersections with the concentric rings per neuron per animal were compared between UN and TR groups. There were significant differences between UN and TR groups in the PH, PAG, CnF, and NTS in the total number of intersections per animal. In some areas, the effect size was smaller when ET was initiated in mature animals, possibly related to their relatively reduced activity levels. In conclusion, the adult rat brain remains dynamic and adapts to chronic ET. However, some brain areas appear to be more affected if ET is initiated in early postnatal development.
[Show abstract][Hide abstract] ABSTRACT: African American men have stiffer large central arteries and impaired dilation of smaller peripheral arteries when compared to their white peers. The purpose of this study was to examine the effect of resistance exercise training (RT) on vascular function and central blood pressure (BP) in young (22 years) African American and white men.
Vascular and hemodynamic measures were made in 19 African American and 18 white men at baseline and following 6-weeks of RT. Carotid BP and carotid/brachial artery beta-stiffness were measured by tonometry and ultrasonography, respectively. Aortic BP was measured by radial artery tonometry and a generalized transfer function. Aortic stiffness was measured by pulse wave velocity (PWV). Forearm blood flow (FBF) was measured by strain-gauge plethysmography before and during reactive hyperemia (RH) induced by 5-min of brachial artery occlusion.
There were similar reductions in central BP and similar increases in FBF-RH in both African American and white men following RT (p<0.05). There were no changes in brachial systolic BP, carotid stiffness, and aortic PWV in either group (p>0.05). There was an increase in brachial stiffness in African American but not white men following RT (p<0.05).
RT led to reductions in central BP and increases in microvascular endothelial function with no effect on central artery stiffness in both groups of young men. RT increased brachial stiffness in African American men. Measurement of conventional brachial BP does not capture the central hemodynamic and vascular response to exercise training due to disparate racial changes in regional vascular properties.
[Show abstract][Hide abstract] ABSTRACT: The pathophysiologic effects of anatoxin-a(s) from the cyanobacterium Anabaena flos-aquae NRC-525-17 were investigated in anaesthetized adult male Sprague Dawley rats given the toxin by continuous intravenous infusion until death. Rats (n=6) pretreated with atropine sulfate (50 mg/kg) intraperitoneally survived significantly longer (P<0.05) than non-atropinized rats (n = 6), suggesting that the muscarinic effects of anatoxin-a(s) were important in the lethal syndrome. In contrast to rats only given toxin, rats that were pretreated with atropine had a decrease in heart rate and mean blood pressure that followed profound reductions in respiratory tidal and minute volume, suggesting that neuromuscular blockade of the muscles of respiration was the cause of death. Even when survival time of rats was increased by pretreatment with atropine, phrenic nerve amplitude increased, indicating a lack of a depressive effect of anatoxin-a(s) on central mediation of respiration. Rats (n=3) continuously ventilated during toxin infusion survived a dose more than 4 fold greater than a consistently lethal dose of the toxin. Thus, the cardiovascular effects of anatoxin-a(s) alone could not account for the death of rats. Electromyographic activity recorded from the diaphragms of rats (n=5) during continuous toxin administration revealed an increase in muscular electrical activity that became more random and finally decreased prior to death, suggesting a toxin-induced neuromuscular blockade in vivo which ultimately was the cause of death of the anatoxin-a(s) dosed rats.
[Show abstract][Hide abstract] ABSTRACT: African Americans have a greater prevalence of hypertension and diabetes compared with white Americans, and both autonomic dysregulation and inflammation have been implicated in the etiology of these disease states. The purpose of this study was to examine the cardiac autonomic and systemic inflammatory response to resistance training in young African-American and white men. Linear (time and frequency domain) and nonlinear (sample entropy) heart rate variability, baroreflex sensitivity, tonic and reflex vagal activity, and postexercise heart rate recovery were used to assess cardiac vagal modulation. C-reactive protein (CRP) and white blood cell count were used as inflammatory markers. Twenty two white and 19 African-American men completed 6 wk of resistance training followed by 4 wk of exercise detraining (Post 2). Sample entropy, tonic and reflex vagal activity, and heart rate recovery were increased in white and African-American men following resistance training (P < 0.05). Following detraining (Post 2), sample entropy, tonic and reflex vagal activity, and heart rate recovery returned to baseline values in white men but remained above baseline in African-American men. While there were no changes in white blood cell count or CRP in white men, these inflammatory markers decreased in African-American men following resistance training, with reductions being maintained following detraining (P < 0.05). In conclusion, resistance training improves cardiac autonomic function and reduces inflammation in African-American men, and these adaptations remained after the cessation of training. Resistance training may be an important lifestyle modification for improving cardiac autonomic health and reducing inflammation in young African-American men.
[Show abstract][Hide abstract] ABSTRACT: Analgesic balms (AB) are widely used in sports medicine. We previously have examined effects of various counterirritant-based AB on pressor responses evoked by muscular contraction (MC), mediated by group III and IV muscle afferents known to produce exercise and nociceptive responses. Our purpose was to examine trolamine salicylate-based analgesic balm (TS) effects.
Ten healthy, adult male and female cats were used. Decerebration under halothane allowed elimination of anesthesia. Electrical stimulation of L7 and S1 ventral roots evoked static MC (30 s). After control runs, commercial TS (10% concentration) was applied to the skin over the contracting muscles of one hind limb (N = 5). MC was evoked every 10 min, alternating between sides. Ipsilateral (T = 0, T + 20, T + 40, T + 60 min) and contralateral (T - 10, T + 10, T + 30, T + 50 min) responses were analyzed. Five additional cats received AB minus TS.
There were significant attenuations in both peak mean arterial pressure (MAP), in the last 12 s and the last 6 s of the 30 s of MC for both contra- and ipsilateral limbs occurring at T + 50 and T + 60 min after TS application, respectively. No significant changes in heart rate (HR) responses were seen for either the ipsi- or contralateral stimulation. There were no changes in MAP or HR in control cats.
These results indicate that TS affects the end of the 30 s of MC, which is thought to be mainly chemically mediated through group IV afferents. TS represents the salicylate class of AB and has no counterirritant properties. TS works as an inhibitor of cyclooxygenase (prostaglandin formation) and is, at least in part, blood borne.
Medicine & Science in Sports & Exercise 12/2007; 39(11):1942-8. DOI:10.1249/mss.0b013e31814fb6b0 · 3.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thyroid hormones play an important role in brain development. In the present study, we examined the influence of transient postnatal hypothyroidism on reproductive neuroendocrine and behavioral outcomes in the male Syrian (golden) hamster. Hamster pups were rendered hypothyroid following exposure to the goitrogen, 6-n-propyl-2-thiouracil (PTU), between postnatal (PN) day 0 (birth) and PN25 (weaning). By 15 days after cessation of PTU, exposure (PN40) serum thyroxine levels had returned to control levels. The testes of treated males were approximately 30% heavier than controls and daily sperm production was increased by 73%. Immunocytochemistry for GnRH revealed that the total number of GnRH neurons did not vary between groups; however, a shift in the distribution of GnRH neurons was observed in treated males such that more GnRH immunoreactive neurons were found in the caudal portion of their normal distribution. The shift in GnRH distribution was associated with a significant reduction (40-50%) in pituitary gonadotropin secretion. Behaviorally, treated males took significantly longer to investigate the anogenital region and then mount a receptive female. A corresponding reduction in the total number of anogenital investigations and mounts was observed. This difference between treated males and controls was reduced, but not eliminated, over successive trials and by the third trial the number of intromission was similar between treated and control males. We conclude that the full complement of adult reproductive functions observed in the male golden hamster requires thyroid hormones during the early postnatal period. The severity of the effects induced by early hypothyroidism in this species varies from transient to permanent, depending on the endpoint.
[Show abstract][Hide abstract] ABSTRACT: It has been shown previously that dendritic branching in cardiorespiratory and locomotor brain areas can be attenuated with exercise training (ET). It was not known whether this process was reversible. Twenty-three (n = 23) male Sprague-Dawley rats were individually caged and divided into two groups: untrained (UN; n = 11) and detrained (DTR; n = 12). DTR were provided with a running wheel at 21 days of age and exercised spontaneously. After 120 days (70 days of ET followed by 50 days of detraining), ET indexes were obtained, including maximal oxygen uptake, percent body fat, resting heart rate, and heart weight-to-body weight ratios. The brain was processed according to a modified Golgi-Cox procedure. Impregnated neurons from the periaqueductal gray (PAG), posterior hypothalamic area (PH), nucleus of the tractus solitarius (NTS), and cuneiform nucleus (CfN) were examined in coronal sections. Neurons were traced using a camera lucida technique and analyzed using the Sholl concentric ring analysis of dendritic branching. t-Tests compared the mean number of intersections per neuron by grouping inner rings, outer rings, and total number of intersections per animal. There were no significant differences between UN and DTR in PH, PAG, CfN, and NTS in the inner rings, outer rings, and total number of intersections per animal. A separate group of animals was used to show that a training effect in the CfN and NTS was present at 56 days of ET. Our results show that dendritic attenuation resulting from 70 days of ET in PH, PAG, CfN, and NTS is completely reversed with 50 days of detraining.