Effect of exercise-induced hyperventilation on airway resistance and cycling endurance

The purpose of the present study was to investigate the effect of exercise induced hyperventilation and hypocapnia on airway resistance (R _aw), and to try to answer the question whether a reduction of R _aw is a mechanism contributing to the increase of endurance time associated with a reduction of exercise induced hyperventilation as for example has been observed after respiratory training. Eight healthy volunteers of both sexes participated in the study. Cycling endurance tests (CET) at 223 (SD 47) W, i.e. at 74 (SD 5)% of the subject's peak exercise intensity, breathing endurance tests and body plethysmograph measurements of pre- and postexercise R _aw were carried out before and after a 4-week period of respiratory training. In one of the two CET before the respiratory training CO₂ was added to the inspired air to keep its end-tidal concentration at 5.4% to avoid hyperventilatory hypocapnia (CO₂-test); the other test was the control. The pre-exercise values of specific expiratory R _aw were 8.1 (SD 2.8), 6.8 (SD 2.6) and 8.0 (SD 2.1) cm H₂O · s and the postexercise values were 8.5 (SD 2.6), 7.4 (SD 1.9) and 8.0 (SD 2.7) cm H₂O · s for control CET, CO₂-CET and CET after respiratory training, respectively, all differences between these tests being nonsignificant. The respiratory training significantly increased the respiratory endurance time during breathing of 70% of maximal voluntary ventilation from 5.8 (SD 2.9) min to 26.7 (SD 12.5) min. Mean values of the cycling endurance time (t _cend) were 22.7 (SD 6.5) min in the control, 19.4 (SD 5.4) min in the CO₂-test and 18.4 (SD 6.0) min after respiratory training. Mean values of ventilation ( _E) during the last 3␣min of CET were 123 (SD 35.8) l · min⁻¹ in the control, 133.5 (SD 35.1) l · min⁻¹ in the CO₂-test and 130.9 (SD 29.1) l · min⁻¹ after respiratory training. In fact, six subjects ventilated more and cycled for a shorter time, whereas two subjects ventilated less and cycled for a longer time after the respiratory training than in the control CET. In general, the subjects cycled longer the lower the _E, if all three CET are compared. It is concluded that R _aw measured immediately after exercise is independent of exercise-induced hyperventilation and hypocapnia and is probably not involved in limiting t _cend, and that t _cend at a given exercise intensity is shorter when _E is higher, no matter whether the higher _E occurs before or after respiratory training or after CO₂ inhalation. Accepted: 11 September 1996     

Effect of glucocorticoids on contractile apparatus of rat skeletal muscle

Skeletal muscles which have a high oxidative potential are less sensitive to the catabolic action of dexamethasone. In fast-twitch white muscles, where the oxidative capacity is low, the alkaline proteinase activity as well as the rise in the number of lysosomes was more pronounced. It seems that the glucocorticoid-caused myopathy is a result of elevated degradation of contractile proteins. This process of degradation of contractile proteins begins in the myosine filaments and then spreads to the thin filaments and the z-line.     

Effect of ACTH and glucocorticoids on plasma prolactin levels in the male rat

Relationships between prolactin and adrenal secretion were studied in the adult male rat by different experimental approaches. Administration of a long acting 1-24 ACTH preparation during 11 days induced a significant decrease in plasma prolactin levels. Adrenalectomy on the contrary resulted in an increase of prolactin levels that were not affected by ACTH treatment. Dexamethasone administration to intact or adrenalectomized animals resulted in a significant reduction of plasma prolactin in both cases. In order to elucidate if the inhibitory effect of the adrenal stimulation on prolactin was mediated through the blockade of endogenous ACTH, stimulation of hypothalamic-pituitary-adrenal axis with chronic intermittent immobilization stress was performed. Stress induced a significant elevation in plasma corticosterone levels, together with a decrease in prolactin values. These data indicated that the inhibitory role of ACTH and stress on prolactin secretion was mediated through the adrenal glucocorticoid stimulation.     

Effect of endurance training on the phospholipid content of skeletal muscles in the rat

Only few data are available on the effect of training on phospholipid metabolism in skeletal muscles. The aim of the present study was to examine the effect of 6 weeks of endurance training on the content of particular phospholipid fractions and on the incorporation of blood-borne [14C]-palmitic acid into the phospholipids in different skeletal muscles (white and red sections of the gastrocnemius, the soleus and the diaphragm) of the rat. Lipids were extracted from the muscles and separated using thin-layer chromatography into the following fractions: sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, cardiolipin and neutral lipids (this fraction being composed mostly of triacylglycerols). It was found that training did not affect the content of any phospholipid fraction in soleus muscle. It increased the content of sphingomyelin in white gastrocnemius muscle, cardiolipin and phosphatidylethanolamine in red gastrocnemius muscle and phosphatidylinositol in white gastrocnemius muscle and diaphragm. The total phospholipid content in red gastrocnemius muscle of the trained group was higher than in the control group. Training reduced the specific activity of sphingomyelin and cardiolipin in all muscles, phosphatidylcholine in soleus, red, and white gastrocnemius muscles, phosphatidylserine in all muscles, phosphatidylinositol in all except the soleus muscle, and phosphatidylethanolamine in hindleg muscles, but not in the diaphragm compared to the corresponding values in the sedentary group. It was concluded that endurance training affects skeletal muscle phospholipid content and the rate of incorporation of the blood-borne [14C]palmitic acid into the phospholipid moieties.     

Effect of metopirone and glucocorticoids on the glycogen content in the adrenals of rat fetuses]

Metopiron, hydrocortisone and dexamethazone are able to influence different links of the hypothalamo-hypohysial-adrenal system and induce the inhibition of glucocorticoid function. Changes in glycogen content in the adrenal gland and liver of rat foetuses under the effect of the drugs in question were studied. It was shown that metopiron exerted no marked influence on the level of glycogen in the adrenal gland and decreased 2.5 times that in the liver. On the contrary, hydrocortisone and dexamethazone increased the glycogen content 2 times in the adrenal gland and did not change that in the liver. The results obtained agree with the hypothesis on the relation between the glycogen level in the adrenal gland and the level of its hormonal activity and are considered as an additional proof of the functioning of hypothalamo-hypophysial-adrenal system during the last days of the rat prenatal development.     

Effect of natural and synthetic glucocorticoids on rat hepatic microsomal drug metabolism

Endogenous and synthetic glucocorticoids of varied biological potency have been used for the treatment of intact male rats in an attempt to determine the interactions of corticosteroids with hepatic mixed-function oxidation. The more potent synthetic steroids increased several components of the microsomal electron transport chain, and the metabolism of biphenyl, aniline, benzo[α]pyrene and ethylmorphine. In contrast, the natural glucocorticoids and their less potent synthetic analogues decreased or had no effect on the activity of these parameters. None of the steroids used affected the spectral interaction kinetics or the apparent K_mvalues of the enzymes responsible for the metabolism of type I and type II substrates. The effects of glucocorticoids on hepatic drug metabolism therefore appear to be different from those of phenobarbital or 3-methylcholanthrene, but show some similarities with those resulting from pregnenolone-16α-carbonitrile or spironolactone pretreatment.     

Effect of endurance training on the sphingomyelin-signalling pathway activity in the skeletal muscles of the rat.

The sphingomyelin signalling pathway has been shown to function in different skeletal muscle types. The aim of the present study was to examine the effect of endurance training on the functioning of the pathway in the muscles. The experiments were carried out on two groups of male Wistar rats: sedentary and trained for six weeks. 24h after cessation of the training rats were anaesthetized and samples of the soleus, red and white section of the gastrocnemius were taken. The content and composition of sphingomyelin-fatty acids and ceramide - fatty acids was determined by means of gas-liquid chromatography. The content of sphingosine and sphinganine was determined by means of high-pressure liquid chromatography. The activity of neutral Mg(++)-dependent sphingomyelinase was determined spectophotometrically using trinitrophenylaminolauroyl-sphingomyelin as the substrate. It has been found that training reduces the total content of sphingomyelin- and ceramide-fatty acids, increases the content of sphinganine and does not affect the content of sphingosine in individual muscle types. The activity of the enzyme in the muscles is also elevated. It is concluded that training affects functioning of the sphingomyelin -signalling pathway in skeletal muscles. The reduction in the content of ceramide may contribute to elevation in glucose uptake in skeletal muscles observed after training.     

Effect of endurance swimming on rat cardiac myofibrillar ATPase with experimental diabetes

Diabetes is characterized by depressed cardiac functional properties attributed to Ca2+-activated ATPase activity. In contrast, endurance swimming enhances the cardiac functional properties and Ca2+-activated myofibril ATPase. Thus, the purpose of this study was to observe if the changes associated with experimental diabetes can be ameliorated with training. Diabetes was induced with a single i.v. injection of streptozotocin (60 mg/kg). Blood and urine glucose concentrations were 802 +/- 44 and 6965 +/- 617 mg/dL, respectively. The training control and training diabetic animals were made to swim (+/- 2% body weight) 4 days/week for 8 weeks. Cardiac myofibril, at 10 microM free Ca2+ concentration was reduced by 54% in the sedentary diabetics compared with sedentary control animals (p less than 0.05). Swim training enhanced the Ca2+-activated myofibril ATPase activities for the normal animals. The diabetic animals, which swam for 8 weeks, had further reduced their Ca2+-activated myofibril ATPase activity when compared with sedentary diabetics (p less than 0.05). Similarly, the Mg2+-stimulated myofibril ATPase activity was depressed by 31% in diabetics following endurance swimming. It is concluded that the depressed Ca2+-activated myofibril ATPase activity of diabetic hearts is not reversible with endurance swimming.     

Contribution of the exercise-induced increment in glucose storage to the increased insulin sensitivity of endurance athletes

The present study was designed to evaluate the contribution of the exercise-induced increment in glucose storage to the increased insulin sensitivity characterizing endurance athletes. Plasma glucose and insulin were measured during an oral glucose tolerance test (OGTT) in six endurance athletes. Glucose storage and lipid oxidation during this test were also determined using indirect calorimetry. These measurements were compared to those obtained in five non-trained subjects who were tested before and during the three days following a 90-min cycle ergometer exercise performed at 69% of their VO2max. As expected, preexercise values of non-trained subjects revealed a much higher insulin response to glucose, and a lower glucose storage and lipid oxidation compared to results obtained in endurance trained individuals. Glucose tolerance was comparable in both groups. The morning following the exercise test, i.e. about 16 h after exercise, glucose storage was significantly increased in non-trained subjects to a level similar to that found in trained subjects. Surprisingly, this was accompanied by higher values of glucose during the OGTT without significant changes in insulinaemia. This impairment in glucose homeostasis was transitory since glucose tolerance had returned to control level on day 2 after exercise. At that time, the increase in glucose storage was less pronounced than in day 1. On day 3 after exercise, glucose and insulin responses to glucose were similar to preexercise values. These results indicate that the increase in glucose storage by acute exercise is not systematically associated with an improved glucose homeostasis, suggesting that other adaptive mechanisms also contribute to the improvement of insulin sensitivity in endurance athletes.     

Effect of glucocorticoids on the oxidative desaturation of fatty acids by rat liver microsomes.

The effect of glucocorticoids on the oxidative desaturation of fatty acids by liver microsomal preparations of rats has been studied. Hydrocortisone produced a significant decrease in the conversion of [1-14C]linoleic acid to gamma-linolenic acid and [1-14C]eicosa-8, 11, 14-trienoic acid to arachidonic acid. Triamcinolone and dexamethasaone were more active than hydrocortisone in depressing delta 6 and delta 5 fatty acid desaturating activity in liver microsomes. The glucocorticoids evoked a maximal response approximately 24 hr after admission. Palmitic acid conversion to palmitoleic acid showed no statistically significant changes by any of the glucocorticoids. The mechanism of action of glucocorticoids is apparently different from other hyperglycemic hormones that produce similar effects.     

Effect of age and endurance training on the capacity for epinephrine-stimulated gluconeogenesis in rat hepatocytes.

The effects of endurance training on hepatic glucose production (HGP) from lactate were examined in 24-h-fasted young (4 mo) and old (24 mo) male Fischer 344 rats by using the isolated-hepatocyte technique. The liver cells were incubated for 30 min with 5 mM lactate ([U-14C]lactate; 25000 dpm/ml) and nine different concentrations of epinephrine (Epi). Basal HGP (with lactate only and no Epi) was significantly greater for young trained (T) (99.6 +/- 6.2 nmol/mg protein) compared with young controls (C) (78.2 +/- 6.0 nmol/mg protein). The basal HGP was also significantly greater for old T (97.3 +/- 5.9 nmol/mg protein) compared with old C (72.2 +/- 3.9 nmol/mg protein). After the incubation with the various concentrations of Epi, Hanes-Woolf plots were generated to determine kinetic constants (Vmax and EC50). Maximal Epi-stimulated hepatic glucose production (Vmax) was significantly greater for young T (142.5 +/- 6.5 nmol/mg protein) compared with young C (110.9 +/- 4.8 nmol/mg protein). Similarly, the Vmax was significantly greater for old T (138.2 +/- 5.0 nmol/mg protein) compared with old C (103.9 +/- 2.5 nmol/mg protein). Finally, there was an increase in the EC50 from the hepatocytes of old T (56.2 +/- 6.2 nM) compared with young T (32.6 +/- 4.9 nM). In like manner, there was an increase in the EC50 from the hepatocytes of old C (59.7 +/- 5.8 nM) compared with young C (33.1 +/- 2.7 nM). The results suggest that training elevates HGP in the basal and maximally Epi-stimulated condition, but with age there is a decline in EC50 that is independent of training status.     

Maternal glucocorticoids increase endotoxin-induced lung inflammation in preterm lambs

Antenatal betamethasone (Beta) is widely used in women with asymptomatic chorioamnionitis at risk for preterm delivery, but its effects on fetal inflammation are unstudied. Groups of ewes at 109 +/- 1 days of gestation received the following treatments: intra-amniotic (IA) saline (control), 0.5 mg/kg intramuscular Beta, 10 mg IA endotoxin (Endo), and Beta + 2 h later Endo (Beta + Endo). Beta suppressed Endo-induced lung inflammation at 1 day. However, compared with Endo 5 days after treatment, Beta + Endo lambs had increased alveolar neutrophils, proinflammatory cytokine mRNA expression, and serum amyloid A3 (SAA3) mRNA expression. IL-1beta mRNA expression was localized to the inflammatory cells, whereas SAA3 mRNA expression was induced in the bronchial epithelium and the inflammatory cells. Compared with Endo, Beta + Endo lambs had increased lung inflammation but equivalent lung volumes 15 days after treatment. The late increase in inflammation in the Beta + Endo animals suggests that glucocorticoids impair the ability of the preterm lung to downregulate Endo-induced inflammation after fetal clearance of the glucocorticoids. These results have implications for lung inflammation and bronchopulmonary dysplasia in preterm infants exposed to chorioamnionitis and maternal glucocorticoids.     

Influence of glucocorticoids on the secretion of pancreatic juice in the rat

The influence of adrenalectomy and hydrocortisone treatment on the exocrine pancreatic secretion has been studied in anaesthetized rats. In the adrenalectomized animals Na+ administered in the saline solution provided for drinking was able to maintain standard sodium levels in serum. In these animals an increase of Na+ secretion in pancreatic juice was observed. Furthermore, the osmotic effect created by the increase in Na+ would account for the increase in pancreatic flow. In these adrenalectomized rats, an increase in K+ output is observed, which can be explained by the high K+ concentrations in serum. Likewise adrenalectomy decreased pancreatic enzyme secretion and produced a loss in weight of the organ that is accounted for by a lack of glucocorticoids. Hydrocortisone administration did not affect neither the secretion nor the weight of the pancreas of the control rats but the hormone proved to be effective in adrenalectomized rats producing a pancreatic secretion close to normal, balancing the secretory rate of water, Na+ and K+, completely restoring total protein secretion and the weight of the pancreas but amylase secretion in part only. It is therefore concluded that the weight of the pancreas and its exocrine secretion are clearly influenced by adrenalectomy and by substitution therapy with hydrocortisone. The administration of this hormone (25 mg.kg-1.day-1 along 6 days) did not affect intact animals.