| 1. |
- Guss, Bengt
(författare)
-
Integrin alpha(V)beta(3) can substitute for collagen-binding beta(1)-integrins in vivo to maintain a homeostatic interstitial fluid pressurel
- 2018
-
Ingår i: Experimental Physiology. - 0958-0670 .- 1469-445X. ; 103, s. 629-634
-
Tidskriftsartikel (refereegranskat)abstract
- Accumulated data indicate that cell-mediated contraction of reconstituted collagenous gels in vitro can serve as a model for cell-mediated control of interstitial fluid pressure (P-IF) in vivo. A central role for collagen-binding beta(1)-integrins in both processes has been established. Furthermore, integrin alpha(V beta 3) takes over the role of collagen-binding beta(1)-integrins in mediating contraction after perturbations of collagen-binding beta(1)-integrins in vitro. Integrin alpha(V beta 3) is also instrumental for normalization of dermal P-IF that has been lowered due to mast cell degranulation with compound 48/80 (C48/80) in vivo. Here we demonstrate a role of integrin alpha(V)beta(3) in maintaining a long term homeostatic dermal P-IF in mice lacking the collagen-binding integrin alpha(111) (alpha 11(-/-) mice). Measurements of P-IF were performed after circulatory arrest. Furthermore, cell-mediated integrin alpha(V)beta(3)-directed contraction of collagenous gels in vitro depends on free access to a collagen site known to bind several extracellular matrix (ECM) proteins that form substrates for (V3)-directed cell attachment, such as fibronectin and fibrin. A streptococcal collagen-binding protein, CNE, specifically binds to and blocks this site on the collagen triple helix. Here we show that whereas CNE perturbed alpha(V beta 3)-directed and platelet-derived growth factor BB-induced normalization of dermal P-IF after C48/80, it did not affect alpha(V beta 3)-dependent maintenance of a homeostatic dermal P-IF. These data imply that dynamic modification of the ECM structure is needed during acute patho-physiological modulations of P-IF but not for long-term maintenance of a homeostatic P-IF. Our data thus show that collagen-binding beta(1)-integrins, integrin alpha(V)beta(3) and ECM structure are potential targets for novel therapy aimed at modulating oedema formation and hypovolemic shock during anaphylaxis.
|
|
| 2. |
- Keramidas, Michail E., et al.
(författare)
-
LunHab : interactive effects of a 10 day sustained exposure to hypoxia and bedrest on aerobic exercise capacity in male lowlanders
- 2017
-
Ingår i: Experimental Physiology. - : John Wiley & Sons. - 0958-0670 .- 1469-445X. ; 102:6, s. 694-710
-
Tidskriftsartikel (refereegranskat)abstract
- NEW FINDINGS: What is the central question of this study? What are the distinct and interactive effects of a 10 day exposure to hypoxia and horizontal bedrest on the whole-body peak oxygen uptake and on the regional cerebral and skeletal muscle tissue oxygenation during upright cycle ergometry in male lowlanders? What is the main finding and its importance? A 10 day sustained exposure to hypoxia aggravates the bedrest-induced reduction in peak oxygen uptake during dynamic exercise engaging large muscle groups, but mitigates the skeletal muscle oxidative capacity impairment elicited by bedrest. The study examined the interactive effects of a 10 day exposure to hypoxia and bedrest on the whole-body peak oxygen uptake (V̇O2 peak ) during maximal exercise and on skeletal muscle and cerebral oxygenation during submaximal exercise. Nine males underwent three 10 day confinements, in a Latin-square order, as follows: (i) a normoxic bedrest [NBR; partial pressure of inspired O2 (PI,O2) = 134.2 ± 0.7 mmHg]; (ii) a hypoxic bedrest (HBR; PI,O2 = 102.9 ± 0.1 mmHg at day 1, 91.5 ± 1.2 mmHg at days 3-10); and (iii) a hypoxic ambulation (HAMB; PI,O2 as in HBR). Before, 1 (R+1) and 3 days (R+3) after each confinement, subjects performed exhaustive, incremental-load and moderate-intensity constant-load (CLTs) cycle-ergometry trials, while breathing either room air or a hypoxic gas mixture. During the CLTs, changes in the regional oxygenation of the cerebral frontal cortex and the vastus lateralis and intercostal muscles were monitored with near-infrared spectroscopy. At R+1, the confinement-related impairment in V̇O2 peak was greater after HBR than after NBR or HAMB, regardless of whether the trial was performed in room air or hypoxia (HBR, -16.2%; NBR, -8.3%; HAMB, -4.1%; P = 0.001). During the CLTs, bedrest aggravated the exercise-induced reduction in locomotor and respiratory muscle oxygenation (P ≤ 0.05); an effect that was less after HBR than after NBR (P ≤ 0.05). The hypoxic exercise-induced cerebral vasodilatory response was blunted by HBR, probably because of the marked hyperventilation-dependent hypocapnia, attendant to the sustained hypoxic stimulus. Hence, short-term exposure to hypoxia potentiates the reduction in V̇O2 peak , but it mitigates the impairment in skeletal muscle oxidative capacity induced by bedrest.
|
|
| 3. |
- Liden, Åsa, et al.
(författare)
-
Integrin αVβ3 can substitute for collagen‐binding β1‐integrins in vivo to maintain a homeostatic interstitial fluid pressure
- 2018
-
Ingår i: Experimental Physiology. - 0958-0670 .- 1469-445X. ; 103:5, s. 629-634
-
Tidskriftsartikel (refereegranskat)abstract
- Accumulated data indicate that cell‐mediated contraction of reconstituted collagenous gels in vitro can serve as a model for cell‐mediated control of interstitial fluid pressure (PIF) in vivo. A central role for collagen‐binding β1‐integrins in both processes has been established. Furthermore, integrin αVβ3 takes over the role of collagen‐binding β1‐integrins in mediating contraction after perturbations of collagen‐binding β1‐integrins in vitro. Integrin αVβ3 is also instrumental for normalization of dermal PIF that has been lowered due to mast cell degranulation with compound 48/80 (C48/80) in vivo. Here we demonstrate a role of integrin αVβ3 in maintaining a long term homeostatic dermal PIF in mice lacking the collagen‐binding integrin α11β1 (α11−/− mice). Measurements of PIF were performed after circulatory arrest. Furthermore, cell‐mediated integrin αVβ3‐directed contraction of collagenous gels in vitro depends on free access to a collagen site known to bind several extracellular matrix (ECM) proteins that form substrates for αVβ3‐directed cell attachment, such as fibronectin and fibrin. A streptococcal collagen‐binding protein, CNE, specifically binds to and blocks this site on the collagen triple helix. Here we show that whereas CNE perturbed αVβ3‐directed and platelet‐derived growth factor BB‐induced normalization of dermal PIF after C48/80, it did not affect αVβ3‐dependent maintenance of a homeostatic dermal PIF. These data imply that dynamic modification of the ECM structure is needed during acute patho‐physiological modulations of PIF but not for long‐term maintenance of a homeostatic PIF. Our data thus show that collagen‐binding β1‐integrins, integrin αVβ3 and ECM structure are potential targets for novel therapy aimed at modulating oedema formation and hypovolemic shock during anaphylaxis.
|
|
| 4. |
- Lindenberger, Marcus, et al.
(författare)
-
Slower lower limb blood pooling in young women with orthostatic intolerance.
- 2015
-
Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 100:1, s. 2-11
-
Tidskriftsartikel (refereegranskat)abstract
- NEW FINDINGS: What is the central question of this study? Orthostatic stress is mostly caused by venous blood pooling in the lower limbs. Venous distension elicits sympathetic responses, and increased distension speed enhances the cardiovascular response. We examine whether lower limb blood pooling rate during lower body negative pressure is linked to orthostatic intolerance. What is the main finding and its importance? A similar amount of blood was pooled in the lower limb, but at a slower rate in women who developed signs of orthostatic intolerance. The difference in blood pooling rate increased with orthostatic stress and was most prominent at a presyncope-inducing level of lower body negative pressure. The findings have implications for the pathophysiology as well as treatment of orthostatic intolerance. Vasovagal syncope is common in young women, but its aetiology remains elusive. Orthostatic stress-induced lower limb blood pooling is linked with central hypovolaemia and baroreceptor unloading. Venous distension in the arm elicits a sympathetic response, which is enhanced with more rapid distension. Our aim was to study both the amount and the speed of lower limb pooling during orthostatic stress and its effects on compensatory mechanisms to maintain cardiovascular homeostasis in women with orthostatic intolerance. Twenty-seven healthy women, aged 20-27 years, were subjected to a lower body negative pressure (LBNP) of 11-44 mmHg. Five women developed symptoms of vasovagal syncope (orthostatic intolerant) and were compared with the remaining women, who tolerated LBNP well (orthostatic tolerant). Lower limb blood pooling, blood flow and compensatory mobilization of venous capacitance blood were measured. Lower body negative pressure induced equal lower limb blood pooling in both groups, but at a slower rate in orthostatic intolerant women (e.g. time to 50% of total blood pooling, orthostatic intolerant 44 ± 7 s and orthostatic tolerant 26 ± 2 s; P < 0.001). At presyncope-inducing LBNP, the mobilization of venous capacitance blood was both reduced (P < 0.05) and much slower in orthostatic intolerant women (P = 0.0007). Orthostatic intolerant women elicited blunted arterial vasoconstriction at low-grade LBNP, activating only cardiopulmonary baroreceptors, while orthostatic tolerant women responded with apparent vasoconstriction (P < 0.0001). In conclusion, slower lower limb blood pooling could contribute to orthostatic intolerance in women. Mobilization of venous capacitance blood from the peripheral to the central circulation was both slower and decreased; furthermore, reduced cardiopulmonary baroreceptor sensitivity was found in women who developed orthostatic intolerance. Further studies including women who experience syncope in daily life are needed.
|
|
| 5. |
- Lucas, Rebekah A. I., et al.
(författare)
-
Age-related changes to cardiac systolic and diastolic function during whole-body passive hyperthermia
- 2015
-
Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 100:4, s. 422-434
-
Tidskriftsartikel (refereegranskat)abstract
- New Findings What is the central question of this study? The effect of ageing on hyperthermia-induced changes in cardiac function is unknown. What is the main finding and its importance? Using echocardiography, we show that during hyperthermia the systolic and diastolic function can be appropriately augmented to meet cardiac demand in healthy older adults, although overall age-related impairments remain. One exception was late diastolic ventricular filling [i.e. E/A ratio and A/(A+E) ratio], which in the older adults was not further augmented during hyperthermia, unlike their young counterparts. To meet cardiac demand, therefore, healthy older adults appear to depend on an increased left ventricular systolic strain and proportion of their cardiac reserve. The effect of ageing on hyperthermia-induced changes in cardiac function is unknown. This study tested the hypothesis that hyperthermia-induced changes in left ventricular systolic and diastolic function are attenuated in older adults when compared with young adults. Eight older (71 +/- 5years old) and eight young adults (29 +/- 5years old), matched for sex, physical activity and body mass index, underwent whole-body passive hyperthermia. Mean arterial pressure (Finometer Pro), heart rate, forearm vascular conductance (venous occlusion plethysmography) and echocardiographic indices of diastolic and systolic function were measured during a normothermic supine period and again after an increase in internal temperature of approximate to 1.0 degrees C. Hyperthermia decreased mean arterial pressure and left ventricular end-diastolic volumes and increased heart rate to a similar extent in both groups (P>0.05). Ageing did not alter the magnitude of hyperthermia-induced changes in indices of systolic (lateral mitral annular S velocity) or diastolic function (lateral mitral annular E velocity, peak early diastolic filling and isovolumic relaxation time; P>0.05). However, with hyperthermia the global longitudinal systolic strain increased in the older group, but was unchanged in the young group (P=0.03). Also, older adults were unable to augment late diastolic ventricular filling [i.e. E/A ratio and A/(A+E) ratio] during hyperthermia, unlike the young (P<0.05). These findings indicate that older adults depend on a greater systolic contribution (global longitudinal systolic strain) to meet hyperthermic demand and that the atrial contribution to diastolic filling was not further augmented in older adults when compared with young adults.
|
|
| 6. |
- Maliqueo, Manuel, et al.
(författare)
-
Acupuncture does not ameliorate metabolic disturbances in the P450 aromatase inhibitor-induced rat model of polycystic ovary syndrome
- 2017
-
Ingår i: Experimental Physiology. - : Wiley-Blackwell Publishing Ltd.. - 0958-0670 .- 1469-445X. ; 102:1, s. 113-127
-
Tidskriftsartikel (refereegranskat)abstract
- Low-frequency electroacupuncture restores sex steroid synthesis and sympathetic activity in women with polycystic ovary syndrome, which may improve its metabolic disturbances likely by modulating sympathetic nerve activity or sex steroid synthesis. We investigated whether low-frequency electroacupuncture regulates the metabolic function to the same extent as treatment with estradiol or -adrenergic blocking in a rat model of polycystic ovary syndrome induced by a P450 aromatase inhibitor (letrozole). Letrozole (β00 μg per day) or placebo pellets were implanted in pre-pubertal Wistar rats. Six weeks thereafter, rats were treated for 5–6 weeks with: low-frequency electroacupuncture (5 days per week), a -adrenergic blocker (propranolol hydrochloride, 0.1 mg kg-1) (5 days per week), or 17-estradiol (β.0 μg) every fourth day. Body weight development, body composition, locomotor activity, insulin sensitivity, tissue specific glucose uptake, lipid profile, adipocyte size, adiponectin and insulin serum concentrations, and gene expression in inguinal fat were measured. All treatments increased circulating levels of LDL-cholesterol. Estradiol treatment restored locomotor activity and increased insulin sensitivity but did not modify the glucose uptake in muscle and fat. An upregulation of genes related to insulin sensitivity and downregulation of genes related to adipogenesis were observed in subcutaneous adipose tissue from rats exposed to letrozole. Only estradiol treatment normalized the expression of these genes. In conclusions, low-frequency electroacupuncture increased LDL-cholesterol without affecting the insulin sensitivity or adipose tissue function, which could suggest effects on hepatic lipid regulation probably mediated by estradiol action or -adrenergic pathway.
|
|
| 7. |
- McDonnell, Adam C., et al.
(författare)
-
The LunHab project : Muscle and bone alterations in male participants following a 10 day lunar habitat simulation.
- 2019
-
Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 104:8, s. 1250-1261
-
Tidskriftsartikel (refereegranskat)abstract
- NEW FINDINGS: What is the central question of this study? It is well established that muscle and bone atrophy in conditions of inactivity or unloading, but there is little information regarding the effect of a hypoxic environment on the time course of these deconditioning physiological systems. What is the main finding and its importance? The main finding is that a horizontal 10 day bed rest in normoxia results in typical muscle atrophy, which is not aggravated by hypoxia. Changes in bone mineral content or in metabolism were not detected after either normoxic or hypoxic bed rest.ABSTRACT: Musculoskeletal atrophy constitutes a typical adaptation to inactivity and unloading of weightbearing bones. The reduced-gravity environment in future Moon and Mars habitats is likely to be hypobaric hypoxic, and there is an urgent need to understand the effect of hypoxia on the process of inactivity-induced musculoskeletal atrophy. This was the principal aim of the present study. Eleven males participated in three 10 day interventions: (i) hypoxic ambulatory confinement; (ii) hypoxic bed rest; and (iii) normoxic bed rest. Before and after the interventions, the muscle strength (isometric maximal voluntary contraction), mass (lean mass, by dual-energy X-ray absorptiometry), cross-sectional area and total bone mineral content (determined with peripheral quantitative computed tomography) of the participants were measured. Blood and urine samples were collected before and on the 1st, 4th and 10th day of the intervention and analysed for biomarkers of bone resorption and formation. There was a significant reduction in thigh and lower leg muscle mass and volume after both normoxic and hypoxic bed rests. Muscle strength loss was proportionately greater than the loss in muscle mass for both thigh and lower leg. There was no indication of bone loss. Furthermore, the biomarkers of resorption and formation were not affected by any of the interventions. There was no significant effect of hypoxia on the musculoskeletal variables. Short-term normoxic (10 day) bed rest resulted in muscular deconditioning, but not in the loss of bone mineral content or changes in bone metabolism. Hypoxia did not modify these results.
|
|
| 8. |
- Nawrot-Porabka, K., et al.
(författare)
-
The role of antisecretory factor in pancreatic exocrine secretion: Studies in vivo and in vitro
- 2015
-
Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 100:3, s. 267-277
-
Tidskriftsartikel (refereegranskat)abstract
- New Findings: What is the central question of this study? Antisecretory factor, an endogenous protein detected in many tissues of the body, is known as an inhibitor of intestinal secretion, but its role in pancreatic exocrine secretory function has not yet been investigated. What is the main finding and its importance? In a rodent model, we show that antisecretory factor reduces pancreatic exocrine secretion, probably via its direct action on the pancreatic acini and via modulation of the enteropancreatic reflexes involving cholecystokinin and sensory nerves. Antisecretory factor (AF) regulates ion and water transport through the intestinal cell membrane. Antisecretory factor inhibits intestinal secretion, but its effect on the exocrine pancreas has not yet been shown. We investigated the effect of AF on pancreatic amylase secretion in vivo and in vitro using pancreatic acini isolated by collagenase digestion. For the in vivo study, Wistar rats were surgically equipped with silicone catheters, inserted into the pancreaticobiliary duct and into the duodenum. Capsaicin was used to deactivate the sensory nerves in turn to assess their involvement in the effects of AF on the exocrine pancreas. Antisecretory factor (1, 3 or 10 μg kg-1 i.p.) was given in basal conditions or following stimulation of pancreatic secretion with diversion of pancreaticobiliary juice. For the in vitro study, rat pancreatic acini were incubated in the presence of increasing doses of AF (from 10-8 to 10-5 m) alone or in combination with caerulein (10-12 m). Cytoplasmic cholecystokinin 1 (CCK1) receptor protein was detected by Western blot and immunoprecipitation studies. Antisecretory factor markedly reduced the output of pancreatic amylase both in basal conditions and when stimulated by diversion of pancreaticobiliary juice. Deactivation of the sensory nerves with capsaicin completely reversed the inhibitory effects of AF on the exocrine pancreas. Caerulein-induced enzyme secretion from the pancreatic acini was inhibited by AF, whereas basal secretion was unaffected. Administration of AF to the rats significantly diminished the synthesis of CCK1 receptor protein. We conclude that AF inhibits pancreatic exocrine secretion indirectly via sensory nerves and directly decreases amylase release from isolated pancreatic acini. The direct inhibitory action of AF on the exocrine pancreas could be related, at least in part, to a reduction of CCK1 receptors on pancreatic acinar cells.
|
|
| 9. |
- Overgaard-Steensen, Christian, et al.
(författare)
-
The frequently used intraperitoneal hyponatraemia model induces hypovolaemic hyponatraemia with possible model-dependent brain sodium loss
- 2016
-
Ingår i: Experimental Physiology. - 0958-0670 .- 1469-445X. ; 101:7, s. 932-945
-
Tidskriftsartikel (refereegranskat)abstract
- Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models, in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (I.P. model). This hyponatraemia model is described as 'dilutional' or 'syndrome of inappropriate ADH (SIADH)', but seminal studies contradict this interpretation. To confront this issue, we developed an I.P. model in a large animal (the pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesized that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single I.V. dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetized and intensively monitored. In vivo brain and muscle water was determined by magnetic resonance imaging and related to the plasma sodium concentration. Muscle water content increased less than expected as a result of pure dilution, and muscle sodium content decreased significantly (by 28%). Sodium was redistributed to the peritoneal fluid, resulting in a significantly reduced plasma volume. This shows that the I.P. model induces hypovolaemic hyponatraemia and not dilutional/SIADH hyponatraemia. Brain oedema evolved, but brain sodium content decreased significantly (by 21%). To conclude, the I.P. model induces hypovolaemic hyponatraemia attributable to sodium redistribution and not water dilution. The large reduction in brain sodium is probably attributable to the specific mechanism that causes the hyponatraemia. This is not accounted for in the current understanding of the brain response to acute hyponatraemia.
|
|
| 10. |
- Siebenmann, Christoph, et al.
(författare)
-
Does cerebral hypoxia facilitate central fatigue?
- 2016
-
Ingår i: Experimental Physiology. - : IEEE Press. - 0958-0670 .- 1469-445X. ; 101:9, s. 1173-1177
-
Tidskriftsartikel (refereegranskat)abstract
- New Findings: What is the topic of this review? This review addresses whether a mismatch between cerebral O2 demand and delivery accelerates the development of central fatigue during endurance-type exercise. What advances does it highlight? The difficulty with studying the importance of cerebral O2 availability for exercise performance is to manipulate cerebral O2 availability independently of muscular O2 availability. The different approaches to overcome this limitation indicate that cerebral oxygenation is not a major limiting factor in normoxia, but may limit performance in submaximal exercise tasks in hypoxia. Central fatigue originates within the central nervous system and is characterized by a decrease in voluntary muscle activation. Reduced systemic O2 availability can facilitate central fatigue by enhancing the afferent input of the chemosensitive nerves that play a pivotal role in development of central fatigue. There is accumulating evidence that, in some situations, inadequate O2 availability to the brain itself promotes central fatigue. This short review presents some of the recent findings supporting a direct effect of inadequate cerebral O2 availability on central fatigue and addresses the persisting limitations.
|
|
