| 1. |
- Mårtensson, Ulrika, et al.
(author)
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Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.
- 2009
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In: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:2, s. 687-98
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Journal article (peer-reviewed)abstract
- In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.
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| 2. |
- Holm, Anders, et al.
(author)
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The G protein-coupled oestrogen receptor 1 agonist G-1 disrupts endothelial cell microtubule structure in a receptor-independent manner.
- 2012
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In: Molecular and Cellular Biochemistry. - : Springer Science and Business Media LLC. - 0300-8177 .- 1573-4919. ; 366:1-2, s. 239-249
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Journal article (peer-reviewed)abstract
- The G protein-coupled oestrogen receptor GPER1, also known as GPR30, has been implicated in oestrogen signalling, but the physiological importance of GPER1 is not fully understood. The GPER1 agonist G-1 has become an important tool to assess GPER1-mediated cellular effects. Here, we report that this substance, besides acting via GPER1, affects the microtubule network in endothelial cells. Treatment with G-1 (3 μM) for 24 h reduced DNA synthesis by about 60 % in mouse microvascular endothelial bEnd.3 cells. Treatment with 3 μM G-1 prevented outgrowth of primary endothelial cells from mouse aortic explants embedded in Matrigel. Treatment with G-1 (0.3-3 μM) for 24 h disrupted bEnd.3 cell and HUVEC microtubule structure in a concentration-dependent manner as assessed by laser-scanning confocal immunofluorescence microscopy. G-1-induced (3 μM) disruption of microtubule was observed also after acute (3 and 6 h) treatment and in the presence of the protein synthesis inhibitor cycloheximide. Disruption of microtubules by 3 μM G-1 was observed in aortic smooth muscle cells obtained from both GPER1 knockout and wild-type mice, suggesting that G-1 influences microtubules through a mechanism independent of GPER1. G-1 dose dependently (10-50 μM) stimulated microtubule assembly in vitro. On the other hand, microtubules appeared normal in the presence of 10-50 μM G-1 as determined by electron microscopy. We suggest that G-1-promoted endothelial cell anti-proliferation is due in part to alteration of microtubule organization through a mechanism independent of GPER1. This G-1-promoted mechanism may be used to block unwanted endothelial cell proliferation and angiogenesis such as that observed in, e.g. cancer.
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| 3. |
- Bansch, Peter, et al.
(author)
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A Model for Evaluating the Effects of Blunt Skeletal Muscle Trauma on Microvascular Permeability and Plasma Volume in the Rat
- 2010
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In: Shock. - 1540-0514. ; 33:4, s. 399-404
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Journal article (peer-reviewed)abstract
- The objective of the present study was to develop an experimental model suitable for studying the effects of a nonhemorrhagic soft tissue trauma on plasma volume (PV) and microvascular permeability. Anesthetized Sprague-Dawley rats were exposed to a sham procedure or a laparotomy followed by a standardized trauma to the abdominal rectus muscle. We evaluated the effects of trauma on transcapillary escape rate and on PV (3 h after trauma) using I-125-albumin as tracer and on edema formation in the traumatized muscle with a wet- versus dry- weight method. The effects of the trauma on the cytokines IFN-gamma, IL-4, IL-6, IL-10, and TNF-alpha were investigated 1 and 3 h after trauma in a separate group. Transcapillary escape rate was 13.9% per hour in the sham animals compared with 18.5% per hour in the traumatized animals (P < 0.05). Because arterial and venous blood pressures were not altered by the trauma, the change in transcapillary escape rate most likely reflects a change in microvascular permeability. Plasma volume decreased from 42 mL/kg at baseline to 31 mL/kg at the end of the experiments (P < 0.05) in the trauma group, whereas PV remained unchanged in the sham group. Only 15% of the PV loss could be referred to edema in the traumatized muscle. Trauma induced a significant increase in IL-6 and IL-10 after 1 h. We conclude that the present nonhemorrhagic trauma induces an increase in microvascular permeability in the traumatized tissue and in other parts of the body, resulting in hypovolemia. The model may be used for the evaluation of different therapeutic interventions aimed at the correction of hypovolemia.
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| 4. |
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| 5. |
- Bansch, Peter, et al.
(author)
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Prostacyclin reduces plasma volume loss after skeletal muscle trauma in the rat.
- 2012
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In: Journal of Trauma and Acute Care Surgery. - 2163-0755.
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Journal article (peer-reviewed)abstract
- BACKGROUND: Trauma induces transcapillary leakage of fluid and proteins because of increased microvascular permeability. Based on studies showing that prostacyclin (PGI2) has permeability-reducing properties, in the present study, we investigated whether PGI2 reduces plasma volume (PV) loss after a nonhemorrhagic trauma. METHODS: The study was performed on anesthetized Sprague-Dawley rats exposed to a controlled standardized blunt trauma to the abdominal rectus muscle. Thereafter, the animals were randomized to treatment with either PGI2 (2 ng/kg per minute) or 0.9% NaCl. PV was estimated before and 3 hours after the trauma using I-albumin as tracer. In separate experiments, the transcapillary escape rate of I-albumin was calculated and plasma concentrations of cytokines were measured after both treatments. RESULTS: Average PV at baseline was 41.6 mL/kg ± 2.5 mL/kg and 42.3 mL/kg ± 1.7 mL/kg in the PGI2 and NaCl animals, respectively. PV was decreased by 22% ± 8% in the NaCl animals and by 11% ± 9% in the PGI2 animals 3 hours after the trauma (p < 0.05). Trauma induced a decrease in mean arterial blood pressure and an increase in hematocrit in both groups. There were no differences in urine production and mean arterial blood pressure between the PGI2 and NaCl animals. The transcapillary escape rate for albumin was calculated for one hour starting 30 minutes after the trauma and was 15.1% ± 2.4% per hour in the PGI2 animals and 17.4% ± 3.3% per hour in the NaCl animals (p = 0.09). Interleukin 6 concentration 3 hours after the trauma was lower in the PGI2 animals than in the NaCl animals (p < 0.05). CONCLUSION: We conclude that PGI2 attenuates PV loss after blunt muscle trauma. The vascular effects of PGI2 are associated with a modulation of the trauma-induced inflammatory response.
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| 6. |
- Bark, Björn, et al.
(author)
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Importance of the Infusion Rate for the Plasma Expanding Effect of 5% Albumin, 6% HES 130/0.4, 4% Gelatin, and 0.9% NaCl in the Septic Rat.
- 2013
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In: Critical Care Medicine. - 1530-0293. ; 41:3, s. 857-866
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Journal article (peer-reviewed)abstract
- OBJECTIVES:: To compare the plasma volume (PV) expanding effect of a fast infusion rate with that of a slow infusion rate of a fixed volume of 5% albumin, of the synthetic colloids, 6% hydroxyethyl starch 130/0.4 and 4% gelatin, and of 0.9% NaCl in a rat sepsis model and to compare the plasma-expanding effect among these fluids. DESIGN:: Prospective, randomized animal study. SETTING:: University hospital laboratory. SUBJECTS:: One hundred and twelve adult male rats. INTERVENTIONS:: Sepsis was induced by cecal ligation and incision followed by closure of the abdomen. After 3 hrs, an infusion of the PV expander under study was started at a volume of 12 mL/kg for the colloids and of 48 mL/kg for 0.9% NaCl, either for 15 mins or for 3 hrs. A control group underwent the same experimental procedure but no fluid was given. MEASUREMENTS AND MAIN RESULTS:: Three hours after start of the infusion (end of experiment), the plasma-expanding effect was better with a slow than a fast infusion rate for the colloids, especially albumin, but the NaCl groups did not differ significantly from the control group. The PV for the control group was 28.7 ± 3 mL/kg. In the slow and the fast infusion groups, it was 38.9 ± 4.3 and 32.6 ± 4.2 mL/kg for albumin (p < 0.001), 32.9 ± 4.3 and 29.5 ± 4.4 mL/kg for hydroxyethyl starch 130/0.4 (p < 0.05), 31.8 ± 3.9 and 28.2 ± 4.1 mL/kg for gelatin (p < 0.05), and 31.8 ± 5.3 and 30.7 ± 6.6 mL/kg for NaCl (n.s), respectively. CONCLUSIONS:: The study showed that the PV expansion by a colloid was greater when given at a slow than at a fast infusion rate, an effect more pronounced for albumin. This difference was not seen for NaCl. The PV-expanding effect was poor for NaCl and better for albumin than for the other colloids.
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| 7. |
- Bark, Björn, et al.
(author)
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Infusion rate and plasma volume expansion of dextran and albumin in the septic guinea pig.
- 2014
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 58:1, s. 44-51
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Journal article (peer-reviewed)abstract
- Intravenous fluid treatment of hypovolaemia in states of increased capillary permeability, e.g. sepsis, is often accompanied by adverse oedema formation. A challenge is therefore to achieve and maintain normovolaemia using as little plasma volume substitution as possible to minimise interstitial oedema. In the present study, we evaluated the importance of infusion rate for the plasma volume expanding effects of 6% dextran 70 and 5% human albumin in a guinea pig sepsis model.
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| 8. |
- Bark, Björn, et al.
(author)
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Plasma Volume Expansion by 0.9% NaCl During sepsis/SIRS, After Hemorrhage, and During a Normal State.
- 2013
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In: Shock. - 1540-0514. ; 40:1, s. 59-64
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine the degree of plasma volume expansion by 0.9% NaCl in relation to the infused volume, in sepsis/SIRS (systemic inflammatory response syndrome), after a standardized hemorrhage, and in a normal condition. DESIGN: Prospective, randomized animal study. SETTING: University hospital laboratory. SUBJECTS: Thirty anesthetized adult male rats. INTERVENTIONS: The study was performed in 3 groups: a sepsis/SIRS group (the S group), in which sepsis/SIRS was induced by cecal ligation and incision, a hemorrhage group (the H group), in which the rats were left without intervention for 4 hrs, and bled 8 mL/kg thereafter. The study also included a group that was left without intervention (the N group). Then, 4 hrs after baseline, all 3 groups were given an infusion of 0.9% NaCl (32 mL/kg) for 15 mins. Baseline was defined as the time point when the surgical preparation was finished. MEASUREMENTS AND MAIN RESULTS: Plasma volumes were measured using I-albumin dilution technique at baseline, after 4 hrs, and 20 mins after the end of infusion. The plasma volume-expanding effect 20 mins after end of infusion was 0.6 ± 2.9% in the S group, 20 ± 6.4% in the H group and 12 ± 11% in the N group, compared to just before start of infusion. CONCLUSIONS: The present study in rats showed that the plasma volume-expanding effect after an infusion of 0.9% NaCl was smaller in a septic/SIRS state than after hemorrhage and in a normal state. This indicates that the plasma volume expanding effect of a crystalloid in sepsis/SIRS is dependent on pathophysiological changes.
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| 9. |
- Bark, Björn, et al.
(author)
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The effect of vitamin C on plasma volume in the early stage of sepsis in the rat.
- 2014
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In: Intensive Care Medicine Experimental. - 2197-425X. ; 2:11
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Journal article (peer-reviewed)abstract
- Previous experimental studies have shown that vitamin C has several beneficial effects in sepsis and burns, such as decreased tissue oedema, improved endothelial barrier function and decreased transcapillary leakage of plasma markers. It has still not been investigated, though, if vitamin C has any impact specifically on plasma volume. The present study aims at testing the hypothesis that vitamin C decreases plasma volume loss in sepsis.
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| 10. |
- Bentzer, Peter, et al.
(author)
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Capillary filtration coefficient is independent of number of perfused capillaries in cat skeletal muscle
- 2001
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In: American Journal of Physiology: Heart and Circulatory Physiology. - 1522-1539. ; 280:6, s. 2697-2706
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Journal article (peer-reviewed)abstract
- The capillary filtration coefficient (CFC) is assumed to reflect both microvascular hydraulic conductivity and the number of perfused capillaries at a given moment (precapillary sphincter activity). Estimation of hydraulic conductivity in vivo with the CFC method has therefore been performed under conditions of unchanged vascular tone and metabolic influence. There are studies, however, that did not show any change in CFC after changes in vascular tone and metabolic influence, and these studies indicate that CFC may not be influenced by alteration in the number of perfused capillaries. The present study reexamined to what extent CFC in a pressure-controlled preparation depends on the vascular tone and number of perfused capillaries by analyzing how CFC is influenced by 1) vasoconstriction, 2) increase in metabolic influence by decrease in arterial blood pressure, and 3) occlusion of precapillary microvessels by arterial infusion of microspheres. CFC was calculated from the filtration rate induced by a fixed decrease in tissue pressure. Vascular tone was increased in two steps by norepinephrine (n = 7) or angiotensin II (n = 6), causing a blood flow reduction from 7.2 +/- 0.8 to at most 2.7 +/- 0.2 ml . min(-1) . 100 g(-1) (P< 0.05). The decrease in arterial pressure reduced blood flow from 4.8 +/- 0.4 to 1.40 +/- 0.1 ml . min(-1) . 100 g(-1) (n = 6). Vascular resistance increased to 990 +/- 260% of control after the infusion of microspheres (n = 6). CFC was not significantly altered from control after any of the experimental interventions. We conclude that CFC under these conditions is independent of the vascular tone and number of perfused capillaries and that variation in CFC reflects variation in microvascular hydraulic conductivity.
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