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Biomedical subjects

R S Mazzeo

Publications and source records attributed to R S Mazzeo.

At least 19 recordsLinked to original sources
PubMed1999

Differential expression of stress proteins in rat myocardium after free wheel or treadmill run training.

High-intensity treadmill exercise increases the expression of a cardioprotective, inducible 72-kDa stress protein (SP72) in cardiac muscle. This investigation examined whether voluntary free wheel exercise training would be sufficient to confer a similar response. Male Sprague-Dawley rats were randomly assigned to either treadmill (TM-Tr) or free wheel (FW-Tr) training groups. By the end of the 8-wk training period, TM-Tr animals ran 1 h/day, 5 days/wk up a 10% grade, covering a distance of 8,282 m/wk. FW-Tr rats ran, on average, 5,300 m/wk, with one-third of the animals covering distances similar to those for the TM-Tr group. At the time of death, hearts of trained and caged sedentary control (Sed) animals were divided into left (LV) and right (RV) ventricles. Citrate synthase activity and the relative immunoblot contents of SP72, SP73 (the constitutive isoform of the SP70 family), and a 75-kDa mitochondrial chaperone (SP75) were subsequently determined. LV and RV did not differ on any measure, and SP73, SP75, and citrate synthase were not affected by training. Cardiac SP72 levels were elevated over fourfold in both ventricles of TM-Tr compared with RV of FW-Sed rats. Despite the animals having run a similar total distance, cardiac SP72 content in FW-Tr rats was not different from that in Sed animals. These data indicate that voluntary exercise training is insufficient to elicit an elevation of SP72 in rat heart and suggest that exercise intensity may be a critical factor in evoking the cardioprotective SP72 response.

Animals↗
PubMed1998

Immune response to a single bout of exercise in young and elderly subjects.

The purpose of this investigation was to examine alterations in lymphocyte proliferation activity and T cell subsets following an acute bout of exercise in young and old subjects. Six young (26+/-3 years) and nine old (69+/-5 years) male subjects were tested at rest and immediately after 20 min of submaximal exercise at 50% peak work capacity. Arterial blood was sampled from an indwelling catheter for catecholamine and immunology assays. Peripheral blood lymphocytes were isolated for mitogen-induced phytohemagglutinin (PHA) proliferation capacity. Lymphocyte subsets were analyzed by dual-labeled flow cytometry. As has been shown in previous studies, baseline proliferative responsiveness was significantly lower in the old (down 22%) compared to the young subjects. In response to submaximal exercise, proliferative responsiveness to PHA increased significantly in the young subjects (up 55%), however, for the old subjects this response did not differ significantly from resting values (up 18%). The number of total lymphocytes, as well as CD4+ and CD8+ T cell subsets, at rest were lower for old subjects compared with young. Exercise-induced increases in T cell subset populations were similar across age groups. It was concluded that, while having lower initial T cell numbers and PHA responsiveness, immunoresponsiveness during a single bout of exercise is, in general, maintained in old when compared to young individuals.

Adult↗
PubMed1998

Poor relationship between arterial [lactate] and leg net release during exercise at 4,300 m altitude.

We evaluated the hypotheses that on acute exposure to hypobaric hypoxia, sympathetic stimulation leads to augmented muscle lactate production and circulating [lactate] through a beta-adrenergic mechanism and that beta-adrenergic adaptation to chronic hypoxia is responsible for the blunted exercise lactate response after acclimatization to altitude. Five control and 6 beta-blocked men were studied during rest and exercise at sea level (SL), on acute exposure to 4,300 m (A1), and after a 3-wk sojourn at altitude (A2). Exercise was by leg cycling at 49% of SL peak O2 consumption (VO2 peak) (65% of altitude VO2 peak or 87 +/- 2.6 W); beta-blockade was by propranolol (80 mg 3x daily), femoral arterial and venous blood was sampled; leg blood flow (Q) was measured by thermodilution, leg lactate net release [ = (2) (1-leg Q) venous-arterial concentrationL] was calculated, and vastus lateralis needle biopsies were obtained. Muscle [lactate] increased with exercise and acute altitude exposure but regressed to SL values with acclimatization; beta-blockade had no effect on muscle [lactate]. Arterial [lactate] rose during exercise at SL (0.9 +/- 0.1 to 1.5 +/- 0.3 mM); exercise at A1 produced the greatest arterial [lactate] (4.4 +/- 0.8 mM), and exercise at A2 an intermediate response (2.1 +/- 0.6 mM). beta-Blockade reduced circulating [lactate] approximately 45% during exercise under all altitude conditions. increased transiently at exercise onset but then declined over time under all conditions. Blood and muscle "lactate paradoxes" occurred independent of beta-adrenergic influences, and the hypotheses relating the blood lactate response at altitude to beta-adrenergic mechanisms are rejected. During exercise at altitude, arterial [lactate] is determined by factors in addition to hypoxemia, circulating epinephrine, and net lactate release from active muscle beds.

Acclimatization↗
PubMed1998

Alterations in myocardial signal transduction due to aging and chronic dynamic exercise.

Normal aging without disease leads to diminished chronotropic and inotropic responses to catecholamine stimulation, resulting in depressed cardiac function with stress. The purpose of this study was to determine molecular mechanisms for decrements in adrenergic responsiveness of the left ventricle (LV) due to aging and to study the effects of chronic dynamic exercise on signal transduction. We measured beta-adrenergic receptor (beta-AR) density, adenylyl cyclase (AC) activity, and G-protein content and distribution in LV from 66 male Fischer 344 rats from three age groups that were either sedentary or treadmill trained (60 min/days, 5 days/wk, 10 wk at 75% of the maximal capacity). Final ages were 7 mo (young), 15 mo (middle-age), and 25 mo (old). There was no significant difference in beta-AR density among groups as a function of age or training. AC production of adenosine 3',5'-cyclic monophosphate (cAMP) with the use of five pharmacological stimulations revealed that old sedentary myocardium had depressed basal, receptor-dependent, G-protein-dependent, and AC catalyst stimulation (30-43%) compared with hearts from young and middle-age sedentary rats. Training did not alter AC activity in either middle-age or old groups but did increase G-protein-dependent cAMP production in young myocardium (12-34%). Immunodetectable concentrations of stimulatory and inhibitory G proteins (Gs and Gi, respectively) showed 43% less total Gs with similar Gi content in hearts from old sedentary compared with middle-age sedentary rats. When compared with young sedentary animals, Gi content was 39 and 50% higher in middle-age sedentary and old sedentary myocardium, respectively. With age, there was a significant shift in the alpha-subunit of Gs distribution from cytosolic fractions of LV homogenates to membrane-bound fractions (8-12% redistribution in middle-age sedentary vs. old sedentary). The most significant training effect was a decrease in Gi content in hearts from old trained rats (23%), which resulted in values comparable with young sedentary rats and reduced the Gi/Gs ratio by 27% in old-rat LV. We report that age-associated reductions in cardiovascular beta-adrenergic responsiveness correspond with alterations in postreceptor adrenergic signaling rather than with a decrease in receptor number. Chronic dynamic exercise partially attenuates these reductions through alterations in postreceptor elements of cardiac signal transduction.

Aging↗
PubMed1998

Catecholamine response during 12 days of high-altitude exposure (4, 300 m) in women.

We have previously demonstrated that acclimatization to high altitude elicits increased sympathetic nerve activity in men. The purpose of this investigation was to determine 1) whether women respond in a similar manner as found previously in men and 2) the extent to which menstrual cycle phase influences this response. Sixteen eumenorrheic women (age, 23.6 +/- 1.2 yr; weight, 56.2 +/- 4. 3 kg) were studied at sea level and during 12 days of high-altitude exposure (4,300 m) in either their follicular (F; n = 11) or luteal (L; n = 5) phase. Twenty-four-hour urine samples were collected at sea level and during each day at altitude. Catecholamines were determined by high-performance liquid chromatography with electrochemical detection. Compared with sea-level values, urinary norepinephrine excretion increased significantly during altitude exposure, peaking on days 4-6. Thereafter, levels remained constant throughout the duration of altitude exposure. The magnitude of this increase was similar between the F (138%) and L (93%) phase. Urinary epinephrine levels were elevated on day 2 of altitude exposure compared with sea-level values for both F and L subjects (93%). Thereafter, urinary epinephrine excretion returned to sea-level values, and no differences were found between F and L subjects. Plasma catecholamine content was consistent with urinary values and supports the concept of an elevation in sympathetic activity over time at altitude. Mean and diastolic blood pressure as well as heart rate adjustments to high altitude correlated significantly with urinary norepinephrine excretion rates. It was concluded that 1) urinary and plasma catecholamine responses to 12 days of high-altitude exposure in women are similar to those previously documented to occur for men; 2) whereas no differences in catecholamine levels were observed between F- and L-phase assignments, for a given urinary norepinephrine excretion rate, blood pressure and heart rates were lower for F vs. L subjects; and 3) several cardiovascular adaptations associated with high-altitude exposure correlated with 24-h urinary norepinephrine excretion rates and thus sympathetic nerve activity.

Adrenal Glands↗
PubMed1998

O2 extraction maintains O2 uptake during submaximal exercise with beta-adrenergic blockade at 4,300 m.

Whole body O2 uptake (VO2) during maximal and submaximal exercise has been shown to be preserved in the setting of beta-adrenergic blockade at high altitude, despite marked reductions in heart rate during exercise. An increase in stroke volume at high altitude has been suggested as the mechanism that preserves systemic O2 delivery (blood flow x arterial O2 content) and thereby maintains VO2 at sea-level values. To test this hypothesis, we studied the effects of nonselective beta-adrenergic blockade on submaximal exercise performance in 11 normal men (26 +/- 1 yr) at sea level and on arrival and after 21 days at 4,300 m. Six subjects received propranolol (240 mg/day), and five subjects received placebo. At sea level, during submaximal exercise, cardiac output and O2 delivery were significantly lower in propranolol- than in placebo-treated subjects. Increases in stroke volume and O2 extraction were responsible for the maintenance of VO2. At 4,300 m, beta-adrenergic blockade had no significant effect on VO2, ventilation, alveolar PO2, and arterial blood gases during submaximal exercise. Despite increases in stroke volume, cardiac output and thereby O2 delivery were still reduced in propranolol-treated subjects compared with subjects treated with placebo. Further reductions in already low levels of mixed venous O2 saturation were responsible for the maintenance of VO2 on arrival and after 21 days at 4,300 m in propranolol-treated subjects. Despite similar workloads and VO2, propranolol-treated subjects exercised at greater perceived intensity than subjects given placebo at 4,300 m. The values for mixed venous O2 saturation during submaximal exercise in propranolol-treated subjects at 4,300 m approached those reported at simulated altitudes >8,000 m. Thus beta-adrenergic blockade at 4,300 m results in significant reduction in O2 delivery during submaximal exercise due to incomplete compensation by stroke volume for the reduction in exercise heart rate. Total body VO2 is maintained at a constant level by an interaction between mixed venous O2 saturation, the arterial O2-carrying capacity, and hemodynamics during exercise with acute and chronic hypoxia.

Adrenergic beta-Agonists↗
PubMed1997

Alterations in key gluconeogenic regulators with age and endurance training.

The purpose of the present investigation was to examine changes in six potential regulators of hepatic gluconeogenesis with normal aging and endurance training: fructose 2,6-bisphosphate (F 2,6-P2), mitochondrial and cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity, PEPCK mRNA, and pyruvate carboxylase and malate dehydrogenase activity. Young (4 months), middle-aged (12 months), and old (22 months) male-Fischer 344 rats (N = 66) were divided into trained and sedentary groups. Trained animals were run 1 h/d, 5 d/wk for 10 weeks at treadmill speeds of 75% age-specific maximal running capacity. Animals were killed at rest, and the right main lobe of the liver was removed. F 2,6-P2 levels were significantly greater in old compared with young animals regardless of training condition (119% and 80% increase in old trained and untrained animals, respectively). No changes were found with training. Rates of cytosolic PEPCK activity declined significantly with age in both trained (1.3 +/- 0.1, 1.0 +/- 0.1, and 0.7 +/- 0.1 mumol/g/min in young, middle-aged, and old, respectively) and untrained (1.3 +/- 0.1, 1.1 +/- 0.1, and 0.8 +/- 0.2 mumol/g/min) groups. Training did not result in any significant differences between age groups. PEPCK gene expression (mRNA) determined by Northern blot analysis decreased 30% in trained and untrained old animals compared to the young counterparts; again, training had no effect in any age group. No significant differences were found in pyruvate carboxylase, mitochondrial PEPCK, or malate dehydrogenase activity with either age or training. These results suggest that previous age-related declines found in hepatic gluconeogenic capacity can be attributed, in part, to changes in F 2,6-P2, cytosolic PEPCK activity, and PEPCK mRNA, but not to alterations in the activities of mitochondrial PEPCK, malate dehydrogenase, or pyruvate carboxylase. Since training had no effect on any regulator studied, the factors responsible for attenuation in the age-related decline in gluconeogenesis with training remain to be determined.

Aging↗
PubMed1997

Plasma catecholamine and lactate relationship during graded exercise in men with spinal cord injury.

Catecholamine and lactate responses to incremental exercise were examined in individuals with spinal cord injury (SCI). Three men with high-level (HINJ) and four with low-level (LINJ) SCI performed VO2peak exercise tests on an arm ergometer. Forearm venous blood samples taken at rest and at the end of each work stage were analyzed for norepinephrine (NE), epinephrine (EPI), and lactate (LA) content. Mann-Whitney tests revealed that peak LA, NE, and EPI responses were greater in LINJ compared with HINJ subjects (LA = 7.1 +/- 0.5 vs 3.2 +/- 0.4 mM; NE = 3.1 +/- 1.0 vs 0.4 +/- 0.1 ng.ml-1; EPI = 0.5 +/- 0.2 vs 0.1 +/- 0.01 ng.ml-1). Spearman rank correlations for LINJ and HINJ groups were NE-EPI, rs = 0.85 vs rs = 0.17; NE-LA, rs = 0.83 vs rs = 0.31; and EPI-LA, rs = 0.73 vs rs = 0.41. The strong relationships between NE, EPI, and LA in the LINJ group were similar to those previously reported in able-bodied athletes. However, the relatively weak association between these factors in the HINJ group indicates that, while some function exits, the sympathoadrenal response to exercise is significantly impaired in these individuals. These results suggest that mechanisms other than catecholamines are primarily responsible for muscle lactate production during incremental exercise in individuals with HINJ.

Adrenal Cortex↗
PubMed1997

Norepinephrine spillover at rest and during submaximal exercise in young and old subjects.

Aging is associated with elevations in plasma norepinephrine concentrations. The purpose of this investigation was to examine total body and regional norepinephrine spillover as an indicator of sympathetic nerve activity. Eight young (26 +/- 3 yr) and seven old (69 +/- 5 yr) male subjects were studied at rest and during 20 min of submaximal cycling exercise at 50% of peak work capacity. Norepinephrine spillover was determined by continuous intravenous infusion of [3H]norepinephrine. Arterial norepinephrine concentrations were significantly greater at rest for old vs. young subjects (280 +/- 36 vs. 196 +/- 27 ng/ml, respectively). Whereas total norepinephrine spillover did not differ between groups at rest, hepatomesenteric norepinephrine spillover was 50% greater in old subjects compared with their young counterparts (51 +/- 7 vs. 34 +/- 5 ng/min, respectively). Additionally, norepinephrine clearance rates at rest were significantly lower for the old subjects (-23%). During exercise, plasma norepinephrine concentrations increased compared with rest, with old subjects again demonstrating greater values than the young group. Hepatomesenteric norepinephrine spillover was significantly greater (+36%) during exercise for old subjects compared with young; however, no difference was found for whole body spillover rates between age groups. Norepinephrine clearance rates remained depressed (-80%) in the old subjects during exercise. Clearance of epinephrine mirrored that for norepinephrine both at rest and during exercise across age groups. It was concluded that in old subjects, a reduction in norepinephrine clearance and an increase in regional norepinephrine spillover can account for the higher plasma norepinephrine concentrations observed at rest. This relationship is not exacerbated by the stress imposed during an acute bout of exercise.

Adult↗
PubMed1997

Relation of sympathetic activation to ventilation in man at 4300 m altitude.

BACKGROUND: The sympathetic nervous activity increases at high altitude but is not maximal initially when hypoxemia is most severe. HYPOTHESIS: The sympathetic activation would correlate better to the ventilatory response to chronic hypoxia than to the severity of hypoxia per se. METHODS: Eleven healthy male volunteers (27 +/- 1 yr) had measurements from the abdominal aorta of pressure, catecholamines, and blood gases at sea level, on arrival at 4300 m, and after 21 d of residence. Additionally, we measured 24-h urinary catecholamine excretion at sea level and each day at altitude, and made serial measurements of resting ventilatory parameters. RESULTS: Arterial norepinephrine (NE) concentrations on arrival at 4300 m were little changed from sea level, but were increased following acclimatization at 21 d. Arterial oxygenation was decreased on arrival, but improved with acclimatization. Arterial epinephrine (E) concentrations were increased on arrival, and returned to an intermediate level by 21 d. The urinary NE excretion was increased along with the increase in VE (p < 0.01) and the fall in end-tidal PCO2 (p < 0.001), but not with the decrease in end-tidal PO2 during the sojourn at 4300 m. Excretion of E did not relate to any ventilatory parameters. Propranolol (240 mg.d-1), which was given to 6 of 11 subjects, did not affect any relationships. CONCLUSION: The sympathetic activation was related to the ventilatory response but not to measures of hypoxemia at 4300 m. We conclude that factors related to ventilatory acclimatization, possibly increased chemoreceptor activity, contribute to the development of sympathetic activation at high-altitude.

Acclimatization↗
PubMed1996

Oxygen consumption in the heart, hepatomesenteric bed, and brain in young and elderly human subjects, and accompanying sympathetic nervous activity.

Although the reduction in whole-body energy expenditure with aging has been well documented, there is little information about the changes that individual organs undergo. We therefore measured oxygen consumption in the heart, hepatomesenteric bed, and brain in elderly subjects and young controls, using central venous catheter techniques and the application of Fick's principle. We also measured whole-body, cardiac, and hepatomesenteric sympathetic nervous activity using isotope dilution methodology. Cardiac, hepatomesenteric, and cerebral oxygen consumption was similar in both groups. Whole-body and hepatomesenteric sympathetic nervous activity was also similar in the study groups, whereas cardiac norepinephrine (NE) spillover was significantly higher in the elderly. In contrast to the young, cardiac sympathetic nervous activity as assessed from NE spillover was not related to either cardiac oxygen consumption or cardiac work in the elderly. The data suggest that although oxygen consumption in the heart, hepatomesenteric bed, and brain are not different between young and elderly individuals, the relationship between sympathetic nervous activity and oxygen consumption in individual organs may alter with aging.

Adult↗
PubMed1996

Hormonal responses to maximal and submaximal exercise in trained and untrained men of various ages.

Neuroendocrine adjustments to maximal and submaximal exercise were investigated in men as a function of age and training status. Twenty-four trained cyclists and 23 sedentary men constituting a young (M = 22.9 yrs, n = 16), middle-aged (M = 44.9 yrs, n = 16), and old (M = 65.5 yrs, n = 15) group performed both a maximal (GXT) and a 45-minute submaximal exercise test (cycle ergometer) at the workload corresponding to their lactate threshold. Plasma lactate, glucose, growth hormone, cortisol, norepinephrine, and epinephrine concentrations were analyzed both at rest and during exercise. Peak oxygen consumption (VO2 peak) was lower with age; however, all trained groups had higher values for VO2 peak compared to sedentary groups, regardless of age. Lactate threshold, when expressed in absolute terms, was lower with advancing age (sedentary decreases 9 and 26%: trained decreases 19 and 35% for middle-age and old, respectively, when compared to young). Pre-exercise plasma norepinephrine levels were higher with age in both trained and sedentary subjects. Cortisol levels were lower with age for sedentary subjects and were significantly elevated in trained subjects across all age groups. Endurance training resulted in increased hormonal responses, as measured by plasma concentrations, to both maximal and submaximal exercise across all age groups. However, regardless of training status, age-related declines were observed in peak responses for lactate, growth hormone, and cortisol during the GXT. During the 45-minute submaximal exercise test, these age-related differences that had been present in the GXT were abolished. This submaximal test represented a lower absolute work load for old compared to young as well as sedentary compared to trained subjects; however, individuals were working at similar relative exercise intensities. We conclude that older individuals are capable of similar hormonal responses to submaximal exercise of identical durations and intensities as their young and middle-aged counterparts, and that chronic endurance training can enhance the hormonal response to exercise in all age groups.

Adult↗
PubMed1996

Hormonal regulation of hepatic gluconeogenesis: influence of age and training.

The contributions of three major gluconeogenic regulators, glucagon (10(-7) M), alpha-adrenergic agonist phenylephrine (10(-5) M), and beta-agonist isoproterenol (10(-5) M) to hepatic glucose synthesis in liver slices from Fischer 344 rats were examined in relation to age and endurance training. Young (4 mo), middle-aged (12 mo), and old (22 mo) male Fischer 344 rats (n = 66) were divided into trained or sedentary groups. Trained animals were run 10 wk on a treadmill at 75% of maximal capacity, 1 h/day, 5 days/wk. Animals were killed at rest, and sections of liver were removed and sliced in a tissue microtome. Slices were incubated in L-[U-14C]lactic acid, Ringer solution, and one of the aforementioned gluconeogenic regulators. Rates of lactate incorporation into glucose and glycogen were significantly greater in young compared with old animals for all three regulators in both trained and untrained animals. Training elicited a 35, 52, and 63% improvement in lactate incorporation into glucose compared with untrained when the livers of young (16.9 +/- 1.2 vs. 10.9 +/- 1.1 mumol.g protein-1.min-1), middle-aged (12.8 +/- 1.3 vs. 6.1 +/- 1.2 mumol.g protein-1.min-1), and old (11.2 +/- 1.1 vs. 4.1 +/- 0.6 mumol.g protein-1.min-1) animals, respectively, were incubated in glucagon. Rates with phenylephrine followed a similar pattern to that with glucagon across age and training, but absolute rates were significantly lower. No training effect in gluconeogenic rate was found when liver was incubated in the presence of isoproterenol. It is concluded that the gluconeogenic capacity of liver declines with age regardless of the gluconeogenic regulator and that training was able to partially offset age-related declines in glucagon-stimulated and alpha-receptor-mediated gluconeogenesis.

Aging↗
PubMed1996

Altitude and beta-blockade augment glucose utilization during submaximal exercise.

To test the hypothesis that altitude exposure increases glucose utilization and that this increment is mediated by a beta-adrenergic mechanism, the effects of hypobaric hypoxia and beta-blockade on glucose rates of appearance (Ra), disappearance (Rd), oxidation (Rox), and leg uptake [G = 2(arteriovenous glucose difference)(1 - leg blood flow)] were measured during rest and a given submaximal exercise task. We studied six healthy beta-blocked (beta) men [26.7 +/- 1.2 (SE) yr, 74.0 +/- 6.6 kg] and five matched controls (C; 26 +/- 1.2 yr, 69.3 +/- 2.6 kg) in energy and nitrogen balance during rest and leg cycle-ergometer exercise at sea level, on acute altitude exposure to 4,300 m (barometric pressure = 463 Torr), and after 3 wk of habituation. Subjects received a primed continuous infusion of [6,6-2H]- and [1-13C]glucose, rested for > or = 90 min, and then immediately exercised for 45 min at 89 W, which elicited 49% of sea-level peak O2 consumption (VO2peak; 65% of altitude VO2peak). At sea level, resting Ra was 1.47 +/- 0.19 and 1.66 +/- 0.16 mg x kg-1 x min-1 for C and beta, respectively, and increased to 3.04 +/- 0.25 and 3.56 +/- 0.27 mg x kg-1 x min-1, respectively, during exercise. Thus glucose Ra was significantly increased by beta-blockade during rest and exercise at sea level. At sea level, beta-blockade increased leg G, which accounted for 49 and 69% of glucose disposal during exercise in C and beta, respectively. On acute altitude exposure, glucose Ra rose significantly during rest and exercise relative to sea level, whereas blockade continued to augment this increment. During exercise on acute exposure, G increased more than at sea level and accounted for a greater percentage (80 and 97%, respectively) of Rd in C and beta during exercise. Similarly, Rox values, particularly during exercise, were increased significantly at altitude relative to sea level, and beta-blockade potentiated this effect. During a given submaximal exercise task after acclimatization, glucose Ra, Rox, and G were increased relative to sea level, but these increments were less than those in response to exercise measured on acute exposure. We conclude that altitude exposure increases glucose use during rest and a given submaximal exercise bout and beta-blockade exaggerates the response.

Adrenergic beta-Antagonists↗
PubMed1995

Effects of age and endurance training on beta-adrenergic receptor characteristics in Fischer 344 rats.

The purpose of this investigation was to examine changes in beta-adrenergic receptor characteristics in various tissues with age and endurance training. Forty-eight young (6 months), middle-aged (15 months), and old (25 months) male Fischer 344 rats were assigned to either a trained or sedentary running group. Animals were endurance trained by 10 weeks of treadmill running at 75% maximal capacity, 1 h/day, 5 days/week. Animals were sacrificed at rest and the heart, liver, and soleus were removed for analysis. Percent of high and low affinity binding sites were determined by competitive binding experiments. Competition curves were generated using 12 concentrations of ICI-89406 (beta 1 antagonist) and ICI-118551 (beta 2 antagonist) to inhibit the total binding of (-) [125I] pindolol (IPIN). Maximal binding site number (Bmax) and affinity (KD) were determined by Scatchard analysis. Heart Bmax did not differ with age or training. An aging effect was observed in liver such that middle-aged and old animals had greater Bmax compared to young animals. In soleus, Bmax was not altered with training but decreased with age. While training had no affect on affinity in the liver and soleus, heart affinity increased with training in both the middle-aged (21%) and old (27%) animals. In soleus, affinity increased but remained unaltered in heart and liver with age. The ratio of beta 1:beta 2 receptors in the heart and liver did not differ with age or training. The influence of age and training on beta-adrenergic receptor characteristics appear to be tissue specific.

Aging↗
PubMed1995

Acclimatization to high altitude increase muscle sympathetic activity both at rest and during exercise.

This investigation examined the relationship between alterations in plasma norepinephrine associated with 21 days of high-altitude exposure and muscle sympathetic activity both at rest and during exercise. Healthy sea level residents, divided into a control group (n = 5) receiving a placebo or a drug group (n = 6) receiving 240 mg/day of propranolol, were studied while at sea level, upon arrival (acute), and after 21 days of residence (chronic) at 4,300 m. Arterial norepinephrine levels and net leg uptake and release of norepinephrine were determine both at rest and during 45 min of submaximal exercise via samples collected from femoral arterial and venous catheters. Arterial norepinephrine levels increased significantly after chronic altitude exposure both at rest (84%) and during exercise (174%) compared with sea level and acute values. A net uptake of norepinephrine was found in resting legs at sea level (0.28 +/- 0.05 nmol/min) and with acute exposure (0.07 +/- 0.06 nmol/min); however, a significant switch to net leg norepinephrine release was observed with chronic altitude exposure (0.51 +/- 0.11 nmol/min). With exercise, a net release of norepinephrine by the leg occurred across all conditions with chronic exposure, again eliciting the greatest values (5.3 +/- 0.6, 8.0 +/- 1.7, and 14.4 +/- 3.1 nmol/min for sea level, acute, and chronic exposure, respectively). It was concluded that muscle sympathetic activity is significantly elevated both at rest and during submaximal exercise as a result of chronic high-altitude exposure, and muscle is a major contributor to the increase in plasma norepinephrine levels associated with prolonged altitude exposure. The presence of dense beta-blockade did not alter this adaptation to altitude.

Acclimatization↗
PubMed1994

Sympathetic response during 21 days at high altitude (4,300 m) as determined by urinary and arterial catecholamines.

The sympathoadrenal system plays a major role in adjustments to both short- and long-term high-altitude exposure. Thus, this study investigated catecholamine responses in blood, urine, and muscle during 3 weeks' exposure to 4,300 m in control and beta-blocked subjects. Eleven healthy, sea level (SL)-resident men (aged 26 +/- 1 years) were studied under resting conditions at SL and on arrival and during 21 days at 4,300 m (Pikes Peak). Six subjects received 240 mg/d propranolol, and five were administered a placebo. Compared with SL values (38.7 +/- 4.3 v 32.4 +/- 2.8 micrograms/d for control and beta-blocked, respectively), urinary norepinephrine (NE) excretion increased significantly during altitude exposure, reaching peak values on days 6 to 7 (105.5 +/- 16.1 v 88.4 +/- 12.3 micrograms/d, respectively). Furthermore, resting arterial NE levels (increases 87%), as well as net NE release (decreases 219%) across the leg, both increased during acclimatization, indicating elevated sympathetic activity. Systemic vascular resistance and arterial pressures increased with time at altitude and correlated with NE measurements. Resting heart rates increased initially and then declined steadily after day 4 at altitude in both groups of subjects. Urinary epinephrine (EPI) excretion increased with initial exposure as compared with SL values (5.1 +/- 0.8 to 6.6 +/- 0.7 micrograms/d for control, 4.5 +/- 0.5 to 5.2 +/- 1.3 micrograms/d for beta-blocked); however, no consistent pattern was observed for the following 20 days at altitude. Arterial EPI increased upon acute exposure, but declined after 21 days' acclimatization. No changes in dopamine excretion were observed with beta-blockade or altitude exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1994

Influence of aging and endurance training on lactate dehydrogenase in liver and skeletal muscle.

The purpose of this investigation was to determine the effects of aging and endurance training on lactate dehydrogenase (LDH) activity and isozyme pattern in liver and skeletal muscle. Male Fischer 344 rats (n = 30) of three different age groups (young, 4 months; middle-aged, 12 months and old, 22 months) were trained on a treadmill at 75% running capacity for 1 h/day, five times per week for 10 weeks. Age-matched sedentary controls (n = 36) were used for comparison. Total LDH enzyme activity was measured spectrophotometrically; LDH isozymes were separated by native 5.5% polyacrylamide gel electrophoresis and quantified densitometrically. With increasing age, hepatic LDH activity decreased 28%. Old sedentary animals displayed significantly less (22%) hepatic LDH 5 than young and middle-aged animals, and significantly more (40%) hepatic LDH 4 than middle-aged animals. Training resulted in a significant decrease (38%) in total hepatic LDH activity in young rats only. Young animals displayed a significant increase in hepatic LDH 3 (28%), whereas middle-aged animals exhibited a significant decrease in hepatic LDH 3 (40%) with training. No change in total hepatic LDH activity was exhibited in middle-aged or old rats with training. Neither aging or training had a significant effect on LDH activity or isozyme pattern in extensor digitorum longus (EDL). Similarly, LDH activity was maintained in soleus with age, and isozyme pattern was only negligibly affected. We conclude that with age there is a decline in hepatic LDH activity and a decrease in the LDH 5 isozyme. Endurance training induced significant decreases in hepatic LDH activity of young animals. However, these decreases were not a result of shifts in isozymal pattern. Further, LDH activity was maintained in EDL and soleus muscle with age. Finally, endurance training did not have a significant effect on LDH activity or isozymal pattern of EDL or soleus.

Adaptation, Physiological↗