Blunted growth hormone response to maximal exercise in middle-aged versus young subjects and no effect of endurance training.

The purpose of this study was to evaluate the GH response to exercise and the effects of endurance training on this response in early middle-aged men. Seven healthy middle-aged [M; 42.0+/-2.4 (+/-SD) yr old] and five young (Y; 21.2+/-1.1 yr old) competition cyclists were investigated before and after 4 months of intensive endurance training. Subjects performed an exhaustive incremental exercise test (50 watts for 3 min) with gas exchange measurement, and blood samples for lactate, glucose, and GH determinations were drawn before exercise, at the end of the exercise, and in the recovery phase (1, 3, 5, 10, 15, 20, and 30 min). Basal insulin-like growth factor I was also determined. At exhaustion no differences were found in relative maximal heart rate or blood lactate and glucose peaks. On the contrary, the two groups had markedly different GH responses; in fact, the peak GH response to exhaustive exercise was much lower in M than in Y (8.1+/-1.3 vs. 57.1+/-15.5 microg/L; P<0.01). The training, similar in subjects of the same group, increased progressively from 182 to 300 km/week (+64.8%) in M and from 350 to 600 km/week (+71.4%) in Y. After the training, the percent increase in maximal oxygen consumption was similar in the two groups (M, +15.2%; Y, +17.5%), confirming that the efficiency of the training performed was comparable. In neither group did training have any effect on the GH peak response to exercise, confirming the blunted GH response in M compared to Y (6.7+/-1.0 vs. 61.0+/-12.9 microg/L; P<0.01). Similarly, insulin-like growth factor I concentrations were not significantly affected by training. In conclusion, active middle-aged subjects, compared with the young, showed a blunted GH response to a physiological stimulus such as exercise, indicating that the age-related decline in GH secretion appears in early middle age. This response was not modified by training in either early middle-aged or young subjects.

Sodium regulating hormones at high altitude: basal and post-exercise levels.

High altitude (HA)-induced diuresis is associated with marked changes in sodium and water regulating hormones, particularly the renin-angiotensin-aldosterone system (RAAS) and atrial natriuretic hormone (ANH). These hormones are also strongly stimulated by physical exercise, which is a major component of daily activity at HA. In spite of the numerous studies in literature, a clear relationship between hormonal changes, HA diuresis, and physical exercise has not yet been established. We therefore evaluated the response of sodium regulating hormones to exhaustive exercise in a group of seven males exposed to prolonged HA hypoxia. The study was divided into four phases: sea level (SL1), after 7 (P1) and after 21 (P2) days at 5050 m (Italian National Research Council Pyramid Laboratory, Nepal), and back at sea level (SL2). At each phase plasma hematocrit (Ht), total body water (TBW), 24-hr sodium excretion (uNa), and urinary volume (uV) were evaluated together with PRA, plasma aldosterone, and ANH, in samples drawn basally from patients in upright position, and at the end of graded step-wise (30 W/2 min) maximal exercise. Levels of uNa and uV were raised at P1 and then declined at P2, with a parallel decrease in TBW and an increase in Ht. Basal PRA and aldosterone levels were suppressed both at P1 and P2 (from 1.9 +/- 0.4 to 0.08 +/- 0.03 and 0.5 +/- 0.1 ng/mL/3 h, and from 7.9 +/- 1.8 to 3.9 +/- 0.4 and 4.5 +/- 0.4 ng/dL, respectively; P < .05). Exhaustive exercise at HA did not induce any significant response in PRA and aldosterone, unlike SL1. Otherwise at P1 ANH levels remained unchanged both basally and during exercise, while at P2 they decreased significantly vs. SL1, both basally and after exercise (from 13.3 +/- 5.7 to 3.5 +/- 1.2 and from 40.2 +/- 10.2 to 17.5 +/- 8.3, respectively; P < .05). Our data show that PRA and aldosterone levels were constantly suppressed at HA and were unresponsive to exercise, whereas the ANH response was significantly stimulated during acute HA exposure, but not during chronic exposure. This suggests that hypoxia-induced chemoreceptor stimulation may cause the natriuretic phenomenon through direct suppression of the RAAS.

A new method for monitoring hydration at high altitude by bioimpedance analysis.

Our study evaluated the performance of a graphical method for monitoring the fluid variation at high altitude in seven adult Caucasian male subjects (average age 25 yr, average height 177 cm). The graphical approach is called the Resistance-Reactance (RXc) graph method and is based on standard bioimpedance analysis (tetrapolar, 50 kHz frequency). Measurements were taken at sea level before the expedition, at 5050 m after 1 wk and 3 wk, and again at sea level after descent. Plasma and urine electrolytes, osmolalities, and the free-water clearance were determined by standard methods. All climbers had baseline impedance vectors within the reference 95% tolerance ellipse for the Italian male population. The high altitude dehydration caused a significant lengthening of vectors, which after descent underwent a significant shortening and returned close to the baseline values. Average urine volume increased by 1.4 l.d-1 in the first week and average body weight decreased by 4.4 kg after 3 wk. The RXc graph method could be useful in the planning of the individual climber's appropriate dehydration and fluid intake at altitude since a feedback control of the hydration is allowed without any assumption of body composition.

Cardiovascular neural regulation during and after prolonged high altitude exposure.

Eight young healthy male subjects, members of a Himalayan expedition, underwent 24 h Holter monitoring before departure, after 1 and 4 weeks at high altitude (5000 m) and after return to sea level. At high altitude, the circadian reciprocal changes in low and high frequency (LF, HF) were absent, with no significant reduction in the LF to HF ratio over the 24 h; moreover, the proportion of adjacent R-R intervals that differed by more than 50 ms (pNN50) decreased significantly and remained lower after return to sea level. Urine catecholamines increased at high altitude, but only norepinephrine, after 1 week of exposure, rose significantly. Upon return to sea level the density, but not the affinity, of [alpha]2-adrenergic receptors on platelets decreased significantly compared to pre-expedition values. At high altitude increased sympathetic activity was indicated by elevation of urine norepinephrine and by the loss of circadian rhythm in spectral components. The simultaneous reduction of HF and pNN50 demonstrated decreased vagal tone. The persistence of increased sympathetic activity could explain the downregulation of adrenergic receptors after prolonged high altitude exposure.

[The effects of enalapril on basal arterial pressure at rest and during exercise and on cardiac performance in hypertensive athletes]. / Effetti dell'enalapril sulla pressione arteriosa basale e da sforzo e sulla performance cardiaca in atleti ipertesi.

A dose of 10 mg of enalapril was administered once a day to regularly trained hypertensive athletes (mean age 39 +/- 8.9 range 29-51) in order to evaluate the effect of the drug on ambulatory blood pressure and on blood pressure and physical performance during stress testing. STUDY DESIGN. This investigation was a randomized, double blind, cross-over versus placebo trial. At first, subjects whose blood pressure met the entry criteria (casual diastolic blood pressure greater than or equal to 95 mmHg), were subjected to 24-hour ambulatory blood pressure monitoring and maximal upright bicycle stress testing including measurement of O2 uptake. Then they were randomly assigned to treatment with placebo or enalapril. After one month they repeated stress testing and then they were crossed over. Stress testing was repeated in all subjects after two months. The 24-hour ambulatory blood pressure monitoring was repeated in all subjects during enalapril treatment only, by a non-blind investigator. RESULTS. Ambulatory blood pressure decreased significantly during enalapril and no changes in heart rate were observed during the monitoring. The results of bicycle stress testing, both in basal and during the placebo test were comparable as regards blood pressure response, maximal workload, effort duration, maximal heart rate and VO2 max. With enalapril systolic and diastolic blood pressure decreased significantly during stress testing both versus basal test and placebo test at each workload considered including maximal workload. No changes were observed during enalapril as regards maximal workload, effort duration, maximal heart rate and VO2 max. CONCLUSION. Our results suggest that enalapril could be effective in treating hypertensive athletes because it reduces blood pressure during physical effort without affecting physical performance. We conclude that enalapril could be considered a first-choice drug in hypertensive athletes doing aerobic sports.

Cordotomy-denervation interactions on contractile and myofibrillar properties of fast and slow muscles in the rat.

Cordotomy-denervation interactions were studied on contractile and myofibrillar properties of slow (soleus) and fast (extensor digitorum longus) muscles of the rat. The spinal cord was transected midthoracically in neonatal (2-day-old) animals. Two months after birth, a unilateral transection of the sciatic nerve was carried out in both cordotomized and control animals. Five weeks after denervation, contractile properties were tested isometrically in vitro; myofibrillar properties were assessed by histochemical staining of the muscle fibers and by electrophoretic analysis of the myosin heavy chain composition. The following results were obtained: (i) In cordotomized animals the contraction time of the soleus was significantly shorter (-23.3% on average) than that in the control animals and this shortening was accompanied by a proportional slow-to-fast shift in myofibrillar properties. (ii) The extensor digitorum longus properties were not significantly different in the control and cordotomized animals. (iii) Denervation in control animals was followed by a marked increase of contraction and half-relaxation times in the extensor digitorum longus, whereas in the soleus only the half-relaxation time was significantly increased; myofibrillar properties in the soleus showed an appreciable slow-to-fast shift, whereas in the fast muscle the main change was an increase in type 2A fibers to the detriment of type 2B. (iv) In cordotomized animals, denervation caused the soleus contraction time to increase to control values, whereas myofibrillar properties shifted to an even faster pattern; in the extensor digitorum longus denervation caused the same changes seen in the control animals. The results showed that cordotomy at birth caused the soleus to develop as a faster muscle than in the control animals. The concurrent effects of cordotomy and denervation on the myofibrillar properties of the soleus suggest that the slow-to-fast change in these properties is a common consequence of the reduction in the level of motor activity. The opposite effects of the two experimental conditions in the soleus contraction time support the view that the contractile alterations that follow denervation mainly reflect alterations in the muscle activation process.

Chronic denervation of rat hemidiaphragm: maintenance of fiber heterogeneity with associated increasing uniformity of myosin isoforms.

During several months of denervation, rat mixed muscles lose slow myosin, though with variability among animals. Immunocytochemical studies showed that all the denervated fibers of the hemidiaphragm reacted with anti-fast myosin, while many reacted with anti-slow myosin as well. This has left open the question as to whether multiple forms of myosin co-exist within individual fibers or a unique, possibly embryonic, myosin is present, which shares epitopes with fast and slow myosins. Furthermore, one can ask if the reappearance of embryonic myosin in chronically denervated muscle is related both to its re-expression in the pre-existing fibers and to cell regeneration. To answer these questions we studied the myosin heavy chains from individual fibers of the denervated hemidiaphragm by SDS PAGE and morphologically searched for regenerative events in the long term denervated muscle. 3 mo after denervation the severely atrophic fibers of the hemidiaphragm showed either fast or a mixture of fast and slow myosin heavy chains. Structural analysis of proteins sequentially extracted from muscle cryostat sections showed that slow myosin was still present 16 mo after denervation, in spite of the loss of the selective distribution of fast and slow features. Therefore muscle fibers can express adult fast myosin not only when denervated during their differentiation but also after the slow program has been expressed for a long time. Light and electron microscopy showed that the long-term denervated muscle maintained a steady-state atrophy for the rat's life span. Some of the morphological features indicate that aneural regeneration events continuously occur and significantly contribute to the increasing uniformity of the myosin gene expression in long-term denervated diaphragm.

[Variations in the resting membrane potential of denervated and tenotomized-denervated rat skeletal muscles]. / Variazioni del potenziale di membrana a riposo in muscoli scheletrici denervati e tenotomizzati-denervati di ratto.

Resting membrane potential (RMP) was studied in denervated (D), tenotomized (T) and tenotomized-denervated (TD) Soleus (S) and Tibialis Anterior (TA) muscles of the rat. In TD muscles, denervation was performed 1 week after tenotomy. The measurements were performed "in vitro" at 20 degrees C, 1-7 days after denervation in D and TD muscles, and 7 days after tenotomy in T muscles. In T muscles there were not differences in comparison with the controls. In D muscles RMP decreased earlier in S than in TA. The time course of membrane depolarization was similar in TD and D muscles until the 2nd day after denervation. At the 3rd day, RMP showed a further, significant reduction in TD muscles, both in S and TA, but not in D muscles. In D muscles, the depolarization increased very slowly up to the 7th day.