Ventilatory responses to exercise and CO2 after menopause in healthy women: effects of age and fitness.

The extent to which aging affects respiratory control in postmenopausal women remains relatively unknown. In a cross-sectional study of 39 postmenopausal women (50-79 years), we examined the influence of age and fitness on the ventilatory responses to hypercapnia (HCVR; +8 mmHg) and exercise (ΔV˙(E)/ΔV˙CO2) above and below the anaerobic threshold (AT). Data were analyzed using the full cohort, by age (younger postmenopausal: YPM, 50-64 years; and older postmenopausal: OPM, 65-79 years) and fitness as per our previous work (Active: V˙O2max ≥90% age-predicted values; and Sedentary: V˙O2max <90% age-predicted values). Although age did not affect the sensitivity of HCVR, Active women had significantly lower HCVR gain compared to sedentary women (Sedentary: 2.12±0.80; Active: 1.57±0.73, p=0.02). In contrast, age, but not fitness, was inversely related to ΔV˙(E)/ΔV˙CO2 above AT (YPM: 46.8±11.5; OPM: 34.8±6.9, p<0.01) which may be explained, at least in part, by age-related declines in lung function. HCVR and ΔV˙(E)/ΔV˙CO2 were not correlated.

Contribution of physical fitness, cerebrovascular reserve and cognitive stimulation to cognitive function in post-menopausal women.

UNLABELLED: Studies of the effects of physical fitness on cognition suggest that exercise can improve cognitive abilities in healthy older adults, as well as delay the onset of age-related cognitive decline. The mechanisms for the positive benefit of exercise and how these effects interact with other variables known to influence cognitive function (e.g., involvement in cognitive activities) are less well understood. The current study examined the associations between the physical fitness, cerebrovascular blood flow regulation and involvement in cognitive activities with neuropsychological function in healthy post-menopausal women. METHODS: Forty-two healthy women between the ages of 55 and 90 were recruited. Physical fitness (V˙O2 max), cerebrovascular reserve (cerebral blood flow during rest and response to an increase in end-tidal (i.e., arterial) PCO2), and cognitive activity (self-reported number and hours of involvement in cognitive activities) were assessed. The association of these variables with neuropsychological performance was examined through linear regression. RESULTS: Physical fitness, cerebrovascular reserve and total number of cognitive activities (but not total hours) were independent predictors of cognitive function, particularly measures of overall cognitive performance, attention and executive function. In addition, prediction of neuropsychological performance was better with multiple variables than each alone. CONCLUSIONS: Cognitive function in older adults is associated with multiple factors, including physical fitness, cerebrovascular health and cognitive stimulation. Interestingly, cognitive stimulation effects appear related more to the diversity of activities, rather than the duration of activity. Further examination of these relationships is ongoing in a prospective cohort study.

Effects of cardiorespiratory fitness and cerebral blood flow on cognitive outcomes in older women.

The mechanisms by which aerobic fitness confers beneficial effects on cognition with aging are unclear but may involve cerebrovascular adaptations. In a cross-sectional study of women from the community (n=42; age range=50-90 years), we sought to determine whether physical fitness is associated with higher cerebrovascular function, and its relationship to cognition. Main outcome measures included resting cerebral blood flow, cerebrovascular reserve, physical fitness (i.e., VO2max) and cognition. Physically fit women had lower resting mean arterial pressure (MAP) and higher cerebrovascular conductance (CVC) than sedentary women. Overall cognition was negatively correlated with age and positively correlated with VO2max. VO2max was a predictor of resting CVC and MAP, and CVC and MAP when end-tidal gases were held constant at near-resting values. MAP and CVC were predictors of cognition. This study identified strong associations between physical fitness, vascular function and cognition, and provides new understanding regarding the mechanisms by which fitness positively impacts cognition with aging. The implications of this research are considerable and warrant future investigation.

Effect of cardiorespiratory fitness on vascular regulation and oxidative stress in postmenopausal women.

Increasing evidence exists suggesting an important role for oxidative stress in the pathogenesis and progression of hypertension in women via a decrease of NO production after menopause. Regular physical training has been shown to upregulate antioxidant enzymatic systems, which may slow down the usual increase of oxidative stress in postmenopausal women. The aims of this study were to determine the impact of fitness status on enzymatic antioxidant efficiency, oxidative stress, and NO production and to determine the associations among oxidative stress, enzymatic antioxidant and NO production, mean arterial blood pressure (MABP), and cerebrovascular conductance (CVC) in postmenopausal women (n=40; 50 to 90 years old). Physical fitness, physical activity, resting MABP, and CVC were measured. End product of NO, lipid peroxidation (malondialdehyde and 8-iso-prostaglandin F2alpha), DNA oxidation (8-hydroxy-2'-deoxyguanosine), protein nitration (nitrotyrosine), antioxidant glutathione peroxidase, and catalase activities were measured in plasma. We identified significant negative associations between oxidative stress and indices of physical fitness (malondialdehyde: r=-0.33, P<0.05; 8-iso-prostaglandin F2alpha: r=-0.39, P<0.05; 8-hydroxy-2'-deoxyguanosine: r=-0.35, P<0.05) and physical activity (malondialdehyde: r=-0.30, P<0.05; 8-iso-prostaglandin F2alpha: r=-0.41, P<0.01; 8-hydroxy-2'-deoxyguanosine: r=-0.39, P<0.05). Conversely, glutathione peroxidase was positively correlated with fitness level (r=0.55; P<0.01). Finally, MABP and CVC were significantly associated with 8-hydroxy-2'-deoxyguanosine (MABP: r=0.36, P<0.05; CVC: r=-0.36, P<0.05), nitrotyrosine (MABP: r=0.39, P<0.05; CVC: r=-0.32, P<0.05), and the end product of NO (MABP: r=-0.57, P<0.01; CVC: r=0.44, P<0.01). These findings demonstrate that, after menopause, fitness level and regular physical activity mediate against oxidative stress by maintaining antioxidant enzyme efficiency. Furthermore, these results suggest that oxidative stress and NO production modulate MABP and CVC.

Relationship between oxidative stress and HIF-1 alpha mRNA during sustained hypoxia in humans.

The aim of this study was to investigate the relations among reactive oxygen species (ROS), hypoxia inducible factor (HIF-1 alpha) gene expression, HIF-1 alpha target gene erythropoietin (EPO), and vascular endothelium growth factor (VEGF) in humans. Five healthy men (32+/-7 years, mean+/-SD) were exposed to 12 h of sustained poikilocapnic hypoxia (P(ET)O(2)=60 mmHg). DNA oxidation (8-hydroxy-2'-deoxyguanosine, 8-OHdG), advanced oxidation protein products (AOPP), EPO, and VEGF were measured in plasma and HIF-1 alpha mRNA was assessed in leukocytes before and after 1, 2, 4, 6, 8, 10, and 12 h of exposure to hypoxia. HIF-1 alpha mRNA amount increased during the first two hours of hypoxic exposure and then returned to baseline levels. The findings reveal an up-regulation of HIF-1 alpha (+68%), VEGF (+46%), and EPO (+74%). AOPP increased continuously from 4 h (+69%) to 12 h (+216%) of hypoxic exposure while 8-OHdG increased after 6 h (+78%) and remained elevated until 12 h. During the "acute" increase phase of HIF-1 alpha (between 0 and 2 h), 8-OHdG was positively correlated with HIF-1 alpha (r=0.55). These findings suggest that hypoxia induces oxidative stress via an overgeneration of reactive oxygen species (ROS). Finally, this study in humans corroborates the previous in vitro findings demonstrating that ROS is involved in HIF-1 alpha transcription.

Effects of acetazolamide on ventilatory, cerebrovascular, and pulmonary vascular responses to hypoxia.

RATIONALE: Acute mountain sickness (AMS) may affect individuals who (rapidly) ascend to altitudes higher than 2,000-3,000 m. A more serious consequence of rapid ascent may be high-altitude pulmonary edema, a hydrostatic edema associated with increased pulmonary capillary pressures. Acetazolamide is effective against AMS, possibly by increasing ventilation and cerebral blood flow (CBF). In animals, it inhibits hypoxic pulmonary vasoconstriction. OBJECTIVES: We examined the influence of acetazolamide on the response to hypoxia of ventilation, CBF, and pulmonary vascular resistance (PVR). METHODS: In this double-blind, placebo-controlled, randomized study, nine subjects ingested 250 mg acetazolamide every 8 h for 3 d. On the fourth test day, we measured the responses of ventilation, PVR, and CBF to acute isocapnic hypoxia (20 min) and sustained poikilocapnic hypoxia (4 h). Ventilation was measured with pneumotachography. Hypoxia was achieved with dynamic end-tidal forcing. The maximum pressure difference across the tricuspid valve (DeltaPmax, a good index of PVR) was measured with Doppler echocardiography. CBF was measured by transcranial Doppler ultrasound. RESULTS: In normoxia, acetazolamide increased ventilation and reduced DeltaPmax, but did not influence CBF. The ventilatory and CBF responses to acute isocapnic hypoxia were unaltered, but the rise in DeltaPmax was reduced by 57%. The increase in DeltaPmax by sustained poikilocapnic hypoxia observed after placebo was reduced by 34% after acetazolamide, the ventilatory response was increased, but the CBF response remained unaltered. CONCLUSIONS: Acetazolamide has complex effects on ventilation, PVR, and CBF that converge to optimize brain oxygenation and may be a valuable means to prevent/treat high-altitude pulmonary edema.