A progressive and reversible decrease of external pH accompanied the catecholamine release elicited by acetylcholine in decorticated bovine adrenal glands perfused with buffer-free Locke solution adjusted to an initial pH of 7.4. Both the secretory response as well as the extracellular acid shift promoted by the cholinergic agonist were antagonized by hexamethonium plus atropine, Mg2+ and verapamil. Experiments performed to assess the effects of the reduction of external pH on acetylcholine-induced release of catecholamines revealed that increasing the extracellular concentration of H+ significantly and reversibly reduced this secretory response. These findings are consistent with the idea that adrenomedullary activation of secretion by acetylcholine could be associated with a transient acidification of the extracellular fluid. This release of protons, arising mainly from the chromaffin granules, may be involved in a local automodulatory mechanism of the regulated secretory process.
Beaury and Eclache (1978) proposed to extrapolate the drift of the heart rate up to maximal heart rate (Hrmax measured during an incremental maximal test) as a convenient way of estimation of the exhaustion tim (tlim) of an exercise at constant power (75 or 80% of Maximal Aerobic Power (MAP)). The purpose of this study was to evaluate this method of estimation of exhaustion time for a large range of power (60, 73, 86, 100 and 120% MAP). We compared the exercise duration calculated with this method (1limtheo) and the actual exhaustion time (tlim). The results showed that the subjects did not reach their maximal heart rate (Hrmax) at tlim and consequently that tlimtheo, calculated by extrapolation of heart rate drift, overestimated tlim, for all the loads in our study. The difference between tlimtheo and tlim (delta tlim expressed as a percentage of tlim) is significantly lower at 86% MAP than delta tlim at the other loads. It is likely that delta tlim is minimal around 80% MAP, i.e. the loads used in the study by Beaury and Eclache (1978). The values of heart rate (Hrlim), oxygen uptake (VO2lim) and oxygen puls (O2pulslim) measured at exhaustion suggested that the high level of energy cost is one of the main limiting factors at 86% MAP, in contrast with other loads.
The purpose of this study was to examine the effect of glutamate-arginine salt (AGs) or placebo (P1) on ammonemia during and after 1 hour exercise on sporting event bicycle under ergonomic device at 80% VO2max in 3 healthy male volunteers (age 18-25 years). Subjects were tested in three sessions, at rest after AGs and during exercise with placebo (Pl) or AGs. The subjects were given 20 g of AGs or Pl orally and 30 min later, exercised at 75-80% VO2max for 30 min. Blood samples were taken at 0, +30, +60, +90, +120 min after AGs and analyzed for ammonemia. Our results show a highly significant increase in plasma ammonia concentration during exercise. The magnitude of this increase was diminished when subjects were given AGs before the exercise session, suggesting that AGs may help reduce physiologic fatigue.
Small doses of NaCN (250 mu g.kg(-1)) intravenously injected into normal anesthetized Wistar rats, provoked immediate hyperventilation, bradycardia and systemic hypotension. These effects resulted mostly from peripheral chemoreceptor (PCR) stimulation. In totally baro- and chemodenervated rats (CDN), the drug induced hypoventilation, reduction in O-2 consumption, prolonged bradycardia and systemic hypotension, characteristics of direct intoxication. In hyperoxic rats, hyperventilation was reduced. Bradycardia was suppressed with reduction in the systemic hypotension, These modifications arose partly from a reduction in PCR excitability and partly from a direct O-2 activity counteracting cyanide poisoning. After chemical sympathetic denervation, rats presented prolonged and enlarged hyperventilation, bradycardia and systemic hypotension due to loss of adaptive baroreflex responses. Cyanide effects are predominantly reflexes in intact rats but these reactions mask the direct toxic effect of the drug which cannot be totally neglected.
Ecto-5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) of mesangial cells may be the main source of adenosine within the glomerulus, and thus essential in the regulation of glomerular microcirculation. c-AMP and c-AMP-stimulating agents were found to induce ecto-5'-nucleotidase of mesangial cells. Dopamine is a catecholamine known to increase c-AMP levels in mesangial cells. We have studied the effect of dopamine on ecto-5'-nucleotidase expression and DNA synthesis of glomerular mesangial cells in culture. Human mesangial cells were exposed to dopamine in the concentration range from 0.1 microM- to 1 mM, for 6-72 h. Ecto-5'-nucleotidase activity of human mesangial cells increased from 118.6 +/- 7.7 to 171 +/- 12 nmol/min/mg in a 72 h culture. This effect was time- and dose-dependent. Cycloheximide, an inhibitor of protein synthesis did not modify basal 5'-nucleotidase activity but it suppressed the stimulatory effect of 10 microM dopamine. DNA synthesis of human mesangial cells, studied after exposure of these cells to the same concentrations of dopamine used in the 5'-nucleotidase stimulation, was inhibited, being also dose dependent. These results indicate that dopamine induces ecto-5'-nucleotidase and inhibits DNA synthesis of cultured human mesangial cells. This action of dopamine on glomerular mesangial cells may be important in the regulation of glomerular hemodynamics.
The effect of medium conditions on the binding of 1-anilino-8-naphthalene sulfonate (ANS) to bovine serum albumin (BSA) was studied. The intensity of binding was affected by the type of the monovalent salts used. While F- and Cl- decreased, SCN- and ClO4- promoted the binding. The relative order in which various anions influence the ANS binding to albumin process followed the lyotropic series. Some changes in the solvent structure affect the extent of binding. Urea exhibited two opposite effects. At low concentration urea induced the binding; at concentration above 1 M the binding was decreased. pH increase between 3 to 6 decreased dramatically primary and secondary sites. At pH higher than 6 only the secondary site affinity was increased. pH effect on the ANS binding to albumin is due to a participation of the acid and neutral conformational change of BSA.
The intestinal absorption of fatty acids proceeds by simple or facilitated diffusion, a mechanism which is affected by temperature. However, most studies in this field have not taken into consideration the fact that birds have higher physiological temperature than mammals, the absorption being studied at 37 degrees C in both cases. The aim of this work has been to find out whether the higher palmitic acid (PA) uptake rate in birds (chickens) compared to mammals (rats) is attributable to the differences between their body temperatures (41.5 degrees C for chickens and 37.5 degrees C for rats). PA-uptake was studied in intestinal (ileal and jejunal) tissue samples of both Hybro broiler chickens (male and female, 4 weeks-old) and Ico:OFA rats (males and females, 8 weeks-old). The intestinal tissue samples were incubated in micellar solution (0.6 mM 14C-PA; 0.3 mM monoolein; 3.4 mM sodium taurodeoxycholate) at 37.5 degrees C and 41.5 degrees C in both cases. Chicken intestinal tissue incorporated PA with higher efficiency at 41.5 degrees C than at 37.5 degrees C. In contrast, increasing the incubation temperature to 41.5 degrees C led to a decrease in PA uptake by female rat intestinal tissue whereas specimens from male rats exhibited the same absorptive efficiency. These results suggest that the incubation temperature determines to some extent the efficiency of fatty acid uptake. However the fact that the temperature caused opposite effects in rats and chickens indicates that the changes in temperature affect the intracellular processing of the fatty acids already taken up rather than the diffusion of fatty acids through the enterocyte brush-border membrane.
Different neurophysiological circuits underlie the various frequencies of the body sway for the regulation of human upright posture. Servo-controlled platforms allowed experimental studies about latency responses after a sudden external disturbance but power frequency repartition during spontaneous dynamic equilibrium has rarely been examined. The purpose of the present study was to examine the zone of sway frequency assigned to proprioceptive afferences from muscular, articular and tendinous receptors in healthy and injured subjects standing on an unstable and minimal area. Dynamic balance conditions were realized by asking athletes to stand up on a seesaw (stabilometer). The recordings (stabilograms) were monitored by means of an accelerometer. Their power spectra were obtained by a fast Fourier transform process. A first study was conducted in order to specify the contribution of articular receptors of the ankle in the regulation of spontaneous dynamic equilibrium of five soccer players with unilateral injured ankle (IA). The balance parameters in lateral sways were measured in monopodal stance on the healthy ankle (HA) comparatively to IA. The stabilogram was longer (P < 0.05), the total energy of 2-20 Hz band (P < 0.01) higher in the IA (1074 +/- 111 mm and 53 +/- 8 V2) than in the HA (836 +/- 150 mm and 36 +/- 8 V2). A second study analyzed the contribution of knee articular receptors involved in the reflexes of antigravity extension. We assessed during bipodal stance the anteroposterior sways of five basketball players with injured knee (IK) and 3 with healthy knee (HK) in eyes-open and eyes-closed situations.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of oxytocin (0.25 IU OT/100 g/d for 3 days) on accessory sex glands structure and catecholamine content were examined in rats kept on two different light regimes.In 12 h light/12 h dark conditions ventral prostate responded to OT by a regression of the epithelial component and an increase in dopamine content. Coagulating gland structure was not affected, but noradrenaline content of the seminal vesicle + coagulating gland complex was enhanced.Constant lighting per se caused atrophic changes in the prostatic epithelium, evident by decreased total volume and by increased percentage of acini containing cuboidal epithelium. OT treatment considerably prevented the epithelial atrophy without affecting catecholamines level. In the seminal vesicle + coagulating gland complex it reduced the dopamine content. Since this light regime elevated the plasma ACTH, the altered accessory sex gland response to OT seems to be due to the stress-induced changes in the neuro-endocrine factors conditioning their function. The effects of OT on accessory glands catecholamine content indicate interferences with their autonomic control.
Diurnal rhythms were studied in three rat liver enzymes of the urea cycle : arginase, arginosuccinate synthetase and arginosuccinase. In animals synchronized to a 12:12 h light-dark cycle these enzymes were determined at 8 different time points under three different feeding schedules : 24 h of fasting, ad libitum feeding and restricted feeding, Under the three experimental conditions maxima of enzyme activities occured during the dark period. In all cases the maximum activity of arginosuccinase preceded the one of arginase and these in turn the one of arginosuccinate synthetase. On the other hand, the hepatic protein level was maximal during the light period and decreased to its lowest level during the dark period. The restriction of food between 08.00 h and 14.00 h induced an important phase shift of hepatic protein rhythm and arginosuccinase activity.Our results suggest that the diurnal rhythms of cytosolic enzymes of the urea cycle are not only dependent on the light-dark cycle, but also on the synchronizing and masking effect of food intake.
In an attempt to assess the possible oxidative stress associated with the transient exercise-induced activation of polymorphonuclear neutrophils (PMN), we compared the effects of eccentric and concentric exercises (downhill run: DR and uphill walk: UW, respectively) of equal duration (35 min) and similar energy cost (60% VO2max) on plasma levels of ascorbic acid ([AA]) and blood concentration of reduced ([GSH]) and oxidized ([GSSG]) glutathione. Eight healthy male subjects took part in this study. Plasma concentration of myeloperoxidase ([MPO]) was used as a specific marker of PMN activation. While there were no significant changes in [MPO] and [AA] in UW experiments, [MPO] increased (+80%) and [AA] decreased significantly during DR tests (P < 0.01 and P < 0.05, respectively). A significant negative relationship was observed between [AA] and [MPO] in DR experiments only (r = -0.49; P < 0.01). Mean (+/- SEM) basal GSH and GSSG concentrations, calculated by pooling the values measured before both tests, were 0.54 +/- 0.02 and 0.12 +/- 0.007 mM, respectively. The blood concentration of these compounds remained practically unchanged in both exercise tests. These results confirm the role played by the eccentric component of muscle contraction in transient exercise-induced PMN activation and suggest that this activation was partly involved in the decrease in [AA] observed in DR experiments. The oxidant stress associated with the exercise protocol used in this study was insufficient to alter blood levels of reduced and oxidized glutathione.
A heuristic model of the relation between blood lactate (L) and VO2 during exercise was used to assess the comparative merits of two methods of reference threshold determination: the habitual linear interpolation method (LT), and a new method using inverse parabolic (second degree) interpolation (PT); the new method capitalizes on the demonstrated curvilinear relation between blood lactate and O2 uptake. Both types of interpolated thresholds were computed, and their error evaluated against the "true" 4-mmol lactate threshold. A combined parametric and Monte Carlo investigation showed that parabolic thresholds are generally superior, being less biased and more precise than their linear counterpart.
The aim of the investigation was to assess whether endogenous triacylglycerol contributes to the maintenance of the atrial functions. To attain this information, the atria from fed and fasted rats were treated with oxfenicine which is a cardioselective inhibitor of carnitine palmitoyltransferase I. In the presence of glucose, oxfenicine suppressed lipolysis without affecting the pacemaker and contractile activities. When exposed to 2-deoxyglucose in a substrate-free medium, the atria displayed a progressive fall of the contractile strength and pacemaker rate. The dysfunctions appeared faster in the atria from fed rats coinciding with a smaller triacylglycerol mobilization. Under this condition, oxfenicine abolished the triacylglycerol breakdown, increased the fall in the peak tension, elicited a rise in the resting tension and accelerated the decline of the pacemaker rate, leading in a significant number of atria to a complete cessation of the spontaneous contractions. These effects proceeded faster in the fed rats atria. Present data suggest that glucose oxidation is sufficient to meet the atrial energy demand when the fatty acid catabolism is impeded. The noxious effects of oxfenicine, attained after the glucose metabolism was eliminated, lend direct evidence to the notion that endogenous triacylglycerol supports, at least partly, the atrial functions.
Rat peritoneal macrophages activated by ionophore A 23187, were labelled after introduction in the culture medium of 1-0-stearoyl 2-0-[3H] arachidonylglycero-3-phosphocholine (as unique source of tritiated arachidonic acid), or [3H] arachidonic acid which was esterified by cells in phospholipids and triglycerides or remained non esterified. With either cell-labelling method, stimulated macrophages produced tritiated nonesterified fatty acids and eicosanoids which were isolated from cell and medium lipids. When introduced into the culture medium at 1, 5 or 10 microM, the membrane phospholipid analogue 1,2 di-O-hexadecylglycerophosphocholine (dihexadecyl-GPC), but not the lysolecithin analogue 1-0-octadecyl 2-0-methylglycero phosphocholine, lowered phospholipase A2 activity with either labelling method. Dihexadecyl-GPC had an inhibitory effect on the release of arachidonic acid and eicosanoids. Moreover, this effect, as measured by tritiated nonesterified fatty acid formation, was greater in activated cells labelled with tritiated phospholipid (IC50 6 microM) than with [3H] arachidonic acid (IC50 60 microM). This is attributable to the inhibitory effect of dihexadecyl-GPC on endogenous phospholipase A2 and the endogenous enzyme excreted together with lysosomes into the medium. It may be concluded that radioactive phospholipid labelling is a sensitive method for measuring phospholipase A2 activity and assessing the effects of potential phospholipase inhibitors.
This study aimed to investigate whether milrinone effect on cardiac muscle contractility undergoes to age-related changes. Experiments were carried out on papillary muscles isolated from right ventricle of Brown Norway rats belonging to two different age groups: 2 month old and 18 month old. The effect of milrinone (10-100 microM) on rat cardiac muscle in vitro preparations was characterized by a reduction of peak developed tension and of contraction duration. Furthermore, the recovery of contractility after a contractile cycle, i.e. the mechanical restitution was faster in the presence of milrinone than in control conditions. All these effects were reduced in preparations from 18 month old rats compared to preparations from 2 month old rats. The decrease of milrinone effect on the mechanical restitution was particularly pronounced. The reduction of the milrinone effects is likely connected with the reduction of the maximal effect of adrenergic stimulation, although the molecular basis of this link is not yet clearly understood.
In anaesthetized rats, intraperitoneal injection of pilocarpine (0.1 to 1 mg.Kg-1) induced a dose-dependent flow of saliva. During salivation by pilocarpine (0.5 mg.Kg-1), the blood content of submaxillary glands was not significantly increased but the blood volume of the animals was reduced. The salivary flow rate induced by pilocarpine was similar in normal and kininogen-deficient rats. L-NG-nitro-arginine (L-NOARG, 35 mg.Kg-1), a nitric oxide synthesis inhibitor, increased the salivary flow elicited by pilocarpine (0.5 mg.Kg-1). L-NOARG did not modify the blood volume loss but decreased the blood content of the submaxillary glands. The volume of salivary secretion induced by isoproterenol (250 mg.Kg-1) was lower in kininogen-deficient rats than in normal rats. It was significantly reduced by HOE 140 (2 mg.Kg-1), a bradykinin antagonist. L-NOARG increased the salivary flow induced by isoproterenol during the ten first minutes of collection but suppressed it thereafter. We concluded that kinins are not involved in the stimulating effect of pilocarpine on rat salivary glands but these peptides would participate to the development of the salivation induced by isoproterenol in rats. Nitric oxide contributes to the control of the vascular tone in rat salivary glands. The influence of L-NOARG on salivation would be explained by its effects on blood pressure and vascular resistances.
The carbohydrate content of pigeon crop secretion called pigeon milk (PM) was in the range of 0.9-1.5%. Sugars of trichloroacetic acid soluble (TCA-S) fraction increased by 67% between day-1 and day-5 of secretion while those of TCA- insoluble (TCA-P) fraction remained fairly constant. Sialic acids constituted 5-9% of carbohydrates. The proportion of lipid- and protein-bound sialic acids was 51% and 31% respectively; the former increased from 41% to 68% between day-1 and day-5 whereas the latter decreased from 45% to 21% during the corresponding period, Some of the sugars of PM were fucose (40%), glucosamine (31%), galactose (12%), mannose (9%) and glucose (8%). The free sugars whose content was very low (0.05%) included fucose, mannose, glucose and some unidentified oligosaccharides. The proportion of lipid- and protein-bound sugars was 31% and 63% respectively; the former decreased by 7% from day-1 to day-5 while the latter increased by 11% during the same period. Gel chromatography of PM confirmed the presence of sialic acids and glucosamine; the latter existed both in free and bound form. The nature of changes in the carbohydrate composition of PM in the first week of secretion was more quantitative than qualitative.
The effects of oleic and elaidic acid upon the in vitro intestinal uptake of cholesterol were studied in 9 weeks-old male and female rats. Elaidic acid increases the uptake of cholesterol when compared to oleic acid in both males and females. It is suggested that elaidic acid may enhance the esterification of cholesterol within the enterocyte through being more available for esterification and/or through being preferentially incorporated into cholesterol esters.
The salivary flow elicited by phenylephrine was reduced in kininogen-deficient rats or by pretreatment of normal Wistar rats with HOE 140, a bradykinin antagonist. Salivary flow induced by substance P was similar in normal and kininogen-deficient rats. Phenylephrine released large amounts of kallikrein in saliva. Isoproterenol was less active while pilocarpine and substance P induced a small secretion of kallikrein. The saliva produced by anaesthetized rats in response to heat stress contained low levels of kallikrein. However a large depletion of the kallikrein content of submaxillary glands was observed in awake animals exposed to 36 degrees C and 40 degrees C for one hour. This depletion was suppressed by prazosin administered with a beta-adrenergic antagonist. Administered alone, these drugs had no effect, whereas atropine increased the depletion. The presence of kallikrein was observed in the oedema fluid which developed around the submaxillary glands in rats pretreated with atropine or exposed to 40 degrees C. A consumption of plasma kininogens occurred during heat exposure. The reflex-induced release of kallikrein during heat exposure is mainly controlled by sympathetic nerves through activation of both alpha and beta-adrenoreceptors. This release induces the formation of kinins which participate to the thermolytic salivation.
