Effects of chronic exercise and deconditioning on platelet function in women

Wang, Jong-Shyan, Chauying J. Jen, and Hsiun-Ing Chen.Effects of chronic exercise and deconditioning on plateletfunction in women. J. Appl. Physiol.83(6): 2080-2085, 1997.To investigate the effects of chronicexercise and deconditioning on platelet function in women, 16 healthysedentary women were divided into control and exercise groups. Theexercise group cycled on an ergometer at 50% maximal oxygenconsumption for 30 min/day, 5 days/wk, for two consecutive menstrualcycles and then were deconditioned for three menstrual cycles. Duringthis period, platelet adhesiveness on a fibrinogen-coated surface,ADP-induced platelet aggregation and intracellular calciumconcentration elevation, guanosine 3,5-cyclic monophosphate (cGMP) content in platelets, and plasma nitric oxide metabolite levels were measured before and immediately after a progressive exercise test in the midfollicular phase. Ourresults indicated that, after exercise training,1) resting heart rates and bloodpressures were reduced, and exercise performance was improved;2) resting platelet function wasdecreased, whereas plasma nitrite and nitrate levels and platelet cGMPcontents were enhanced; and 3) thepotentiation of platelet function by acute strenuous exercise wasdecreased, whereas the increases in plasma nitrite and nitrate levelsand platelet cGMP contents were enhanced by acuteexercise. Furthermore, deconditioning reversed these training effects. This implies that training-induced platelet functional changes in women in the midfollicular phase may be mediatedby nitric oxide.

     

Severe exercise and exercise training exert opposite effects on human neutrophil apoptosis via altering the redox status

Neutrophil spontaneous apoptosis, a process crucial for immune regulation, is mainly controlled by alterations in reactive oxygen species (ROS) and mitochondria integrity. Exercise has been proposed to be a physiological way to modulate immunity; while acute severe exercise (ASE) usually impedes immunity, chronic moderate exercise (CME) improves it. This study aimed to investigate whether and how ASE and CME oppositely regulate human neutrophil apoptosis. Thirteen sedentary young males underwent an initial ASE and were subsequently divided into exercise and control groups. The exercise group (n = 8) underwent 2 months of CME followed by 2 months of detraining. Additional ASE paradigms were performed at the end of each month. Neutrophils were isolated from blood specimens drawn at rest and immediately after each ASE for assaying neutrophil spontaneous apoptosis (annexin-V binding on the outer surface) along with redox-related parameters and mitochondria-related parameters. Our results showed that i) the initial ASE immediately increased the oxidative stress (cytosolic ROS and glutathione oxidation), and sequentially accelerated the reduction of mitochondrial membrane potential, the surface binding of annexin-V, and the generation of mitochondrial ROS; ii) CME upregulated glutathione level, retarded spontaneous apoptosis and delayed mitochondria deterioration; iii) most effects of CME were unchanged after detraining; and iv) CME blocked ASE effects and this capability remained intact even after detraining. Furthermore, the ASE effects on neutrophil spontaneous apoptosis were mimicked by adding exogenous H₂O₂, but not by suppressing mitochondrial membrane potential. In conclusion, while ASE induced an oxidative state and resulted in acceleration of human neutrophil apoptosis, CME delayed neutrophil apoptosis by maintaining a reduced state for long periods of time even after detraining.     

Cellular Responses to Mechanical Stress: Invited Review: Effects of flow on vascular endothelial intracellular calcium signaling of rat aortas ex vivo

To study the effects of flow on in situendothelial intracellular calcium concentration([Ca²⁺]_i) signaling, rat aortic rings wereloaded with fura 2, mounted on a tissue flow chamber, and divided intocontrol and flow-pretreated groups. The latter was perfused with bufferat a shear stress of 50 dyns/cm² for 1 h. Endothelial[Ca²⁺]_i responses to ACh or shear stresseswere determined by ratio image analysis. Moreover, ACh-induced[Ca²⁺]_i elevation responses were measured ina calcium-free buffer, or in the presence of SKF-96365, to elucidatethe role of calcium influx in the flow effects. Our results showed that1) ACh increased endothelial[Ca²⁺]_i in a dose-dependent manner, and theseresponses were incremented by flow-pretreatment; 2) thedifferences in ACh-induced [Ca²⁺]_i elevationbetween control and flow-pretreated groups were abolished by SKF-96365or by Ca²⁺-free buffer; and 3) in the presenceof 10⁵ M ATP, shear stress induced dose-dependent[Ca²⁺]_i elevation responses that were notaltered by flow-pretreatment. In conclusion, flow-pretreatment augmentsthe ACh-induced endothelial calcium influx in rat aortas ex vivo.

     

Lysophosphatidylcholine alters vascular tone in rat aorta by suppressing endothelial [Ca<Superscript>2+</Superscript>]<Subscript>i</Subscript> signaling

The detailed mechanism of how lysophosphatidylcholine (LPC) suppresses endothelium-dependent vasodilatation is unclear at present. We investigated the effects of LPC on endothelial intracellular calcium (EC [Ca(2+)](i)) signaling and vascular tone simultaneously using a new technique we developed. Fura-2-labeled rat aortic specimens were mounted in a tissue flow chamber and precontracted with phenylephrine (5 x 10(-8) M). Under either basal or agonist-stimulated conditions, the EC [Ca(2+)](i) level was calculated from fura 2 fluorescence ratio images, and the vascular tone was estimated by measuring the relative displacement of the fluorescence images. Although both acetylcholine (ACh)-induced EC [Ca(2+)](i) elevation and the concomitant vasorelaxation were partially suppressed in specimens pretreated with LPC (20 microM), the quantitative relationship between EC [Ca(2+)](i) elevation and the corresponding vasorelaxation was unaffected. A high concentration of LPC (40 microM) completely eliminated ACh-evoked [Ca(2+)](i) elevation and vasodilatation. It has been reported that exposing vascular tissue to a calcium-free buffer causes a reduction in the EC [Ca(2+)](i) level and the accompanying vasoconstriction. Pretreatment with 20 microM LPC reduced the basal EC [Ca(2+)](i) level and abolished the calcium-free solution-induced EC [Ca(2+)](i) reduction and vasoconstriction. We conclude that LPC impairs endothelium-dependent vasorelaxation mainly by reducing the basal EC [Ca(2+)](i) level and suppressing agonist-evoked EC [Ca(2+)](i) signaling.     

Short-term exercise training improves vascular function in hypercholesterolemic rabbit femoral artery

Chronic exercise in healthy or hypercholesteremic animals for at least two months improves their vascular functions. This study is to examine whether short-term exercise training protocols can correct early-stage vascular dysfunction induced by high-cholesterol diet feeding. Male New Zealand White rabbits were fed for 2, 4 or 6 weeks with rabbit chow with or without the addition of 2% (w/w) cholesterol. They were further divided into control and exercise groups. Animals in exercise groups ran on a leveled treadmill for the same time periods as diet intervention. At the end of experiments, femoral arteries were dissected, loaded with fura 2-AM, and mounted in a tissue flow chamber. Phenylephrine-precontracted vessel specimens were exposed to acetylcholine. The endothelial intracellular calcium elevation and vasorelaxation were determined simultaneously under an epifluorescence microscope with ratio imaging capability. En face oil red O staining was used to evaluate fatty streak formation. Our results showed that 1) high-cholesterol diet feeding for > or = 4 weeks caused lipid deposition, reduced the acetylcholine-evoked endothelial calcium signaling, and impaired both endothelium-dependent and endothelium-independent vascular responses in a time-dependent manner; 2) vasorelaxation at given levels of endothelial intracellular calcium elevation decreased in hypercholesterolemia; 3) concomitant exercise program had reverse effects. We conclude that high-cholesterol diet intervention for as short as 4 weeks induces vascular structural changes, impairs endothelial intracellular calcium signaling and vasodilatation in rabbit femoral arteries. Short-term exercise training in parallel completely eliminates these adverse effects so long as the diet intervention is no more than 6 weeks.     

Chronic treadmill exercise in rats delicately alters the Purkinje cell structure to improve motor performance and toxin resistance in the cerebellum

Although exercise usually improves motor performance, the underlying cellular changes in the cerebellum remain to be elucidated. This study aimed to investigate whether and how chronic treadmill exercise in young rats induced Purkinje cell changes to improve motor performance and rendered the cerebellum less vulnerable to toxin insults. After 1-wk familiarization of treadmill running, 6-wk-old male Wistar rats were divided into exercise and sedentary groups. The exercise group was then subjected to 8 wk of exercise training at moderate intensity. The rotarod test was carried out to evaluate motor performance. Purkinje cells in cerebellar slices were visualized by lucifer yellow labeling in single neurons and by calbindin immunostaining in groups of neurons. Compared with sedentary control rats, exercised rats not only performed better in the rotarod task, but also showed finer Purkinje cell structure (higher dendritic volume and spine density with the same dendritic field). The exercise-improved cerebellar functions were further evaluated by monitoring the long-lasting effects of intraventricular application of OX7-saporin. In the sedentary group, OX7-saporin treatment retarded the rotarod performance and induced ～60% Purkinje cell loss in 3 wk. As a comparison, the exercise group showed much milder injuries in the cerebellum by the same toxin treatment. In conclusion, exercise training in young rats increased the dendritic density of Purkinje cells, which might play an important role in improving the motor performance. Furthermore, as Purkinje cells in the exercise group were relatively toxin resistant, the exercised rats showed good motor performance, even under toxin-treated conditions.     

Acute exercise enhances vasorelaxation by modulating endothelial calcium signaling in rat aortas

The role of endothelial calcium signaling in exercise-enhanced ACh-induced vasorelaxation was examined using male Wistar rats (8~10 wk old) that were divided into control and exercise groups. The exercised animals ran on a treadmill with progressive increments of speed until exhaustion. After decapitation, aortic rings were dissected and loaded with fura 2-AM. After being mounted on a tissue flow chamber, vessels were precontracted with phenylephrine, and ACh-induced endothelial calcium elevation and vasorelaxation were determined simultaneously under an epifluorescence microscope equipped with ratio imaging capability. Our results showed that 1) there was logarithmic correlation between endothelial calcium elevation and vasorelaxation; 2) acute exercise enhanced ACh-induced endothelial calcium elevation and vasorelaxation without altering their relationship; 3) pretreatment with N(omega)-nitro-L-arginine markedly reduced ACh-induced vasorelaxation in both groups but suppressed the calcium response only in the exercise group; and 4) the exercise effect on endothelial calcium elevation was abolished by Ca2+-free buffer or gadolinium. In conclusion, acute exercise increases ACh-induced vasorelaxation by increasing the endothelial calcium influx and the calcium-dependent nitric oxide release.