| 1. |
- Aalkjær, Christian, et al.
(författare)
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Sympathetic and Sensory-Motor Nerves in Peripheral Small Arteries.
- 2021
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Ingår i: Physiological reviews. - : American Physiological Society. - 1522-1210 .- 0031-9333. ; 101:2, s. 495-544
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Forskningsöversikt (refereegranskat)abstract
- Small arteries, which play important roles in controlling blood flow, blood pressure, and capillary pressure, are under nervous influence. Their innervation is predominantly sympathetic and sensory motor in nature, and while some arteries are densely innervated, others are only sparsely so. Innervation of small arteries is a key mechanism in regulating vascular resistance. In the second half of the previous century, the physiology and pharmacology of this innervation were very actively investigated. In the past 10-20yr, the activity in this field was more limited. With this review we highlight what has been learned during recent years with respect to development of small arteries and their innervation, some aspects of excitation-release coupling, interaction between sympathetic and sensory-motor nerves, cross talk between endothelium and vascular nerves, and some aspects of their role in vascular inflammation and hypertension. We also highlight what remains to be investigated to further increase our understanding of this fundamental aspect of vascular physiology.
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| 2. |
- Abudula, R, et al.
(författare)
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Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K(+)-channels.
- 2008
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Ingår i: Diabetes, obesity & metabolism. - : Wiley. - 1463-1326 .- 1462-8902.
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we showed that rebaudioside A potently stimulates the insulin secretion from isolated mouse islets in a dose-, glucose- and Ca(2+)-dependent manner. Little is known about the mechanisms underlying the insulinotropic action of rebaudioside A. The aim of this study was to define the signalling system by which, rebaudioside A acts. Isolated mouse islets were used in the cAMP[(125)I] scintillation proximity assay to measure total cAMP level, and in a luminometric method to measure intracellular ATP and ADP concentrations. Conventional and permeabilized whole-cell configuration of the patch-clamp technique was used to verify the effect of rebaudioside A on ATP-sensitive K(+)-channels from dispersed single beta cells from isolated mouse islets. Insulin was measured by radioimmunoassay from insulinoma MIN6 cells. In the presence of 16.7 mM glucose, the addition of the maximally effective concentration of rebaudioside A (10(-9) M) increased the ATP/ADP ratio significantly, while it did not change the intracellular cAMP level. Rebaudioside A (10(-9) M) and stevioside (10(-6) M) reduced the ATP-sensitive potassium channel (K(ATP)) conductance in a glucose-dependent manner. Moreover, rebaudioside A stimulated the insulin secretion from MIN6 cells in a dose- and glucose-dependent manner. In conclusion, the insulinotropic effect of rebaudioside A is mediated via inhibition of ATP-sensitive K(+)-channels and requires the presence of high glucose. The inhibition of ATP-sensitive K(+)-channels is probably induced by changes in the ATP/ADP ratio. The results indicate that rebaudioside A may offer a distinct therapeutic advantage over sulphonylureas because of less risk of causing hypoglycaemia.
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| 3. |
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| 4. |
- Boedtkjer, D M Briggs, et al.
(författare)
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Vasomotion has chloride-dependency in rat mesenteric small arteries.
- 2008
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Ingår i: Pflügers Archiv : European journal of physiology. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 457:2, s. 389-404
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Tidskriftsartikel (refereegranskat)abstract
- The possibility that Ca(2+)-activated Cl(-) conductances (CaCCs) contribute to oscillations in vascular tone (vasomotion) is tested in isolated mesenteric small arteries from rats where cGMP independent (I (Cl(Ca))) and cGMP-dependent (I (Cl(Ca,cGMP))) chloride conductances are important. The effect of anion substitution and Cl(-) channel blockers on noradrenaline (NA)-stimulated tension in isometrically mounted mesenteric arteries and for chloride conductance of smooth muscle cells isolated from these arteries were assessed electrophysiologically. Cl(-) (o) replacement with aspartate blocked vasomotion while 36mM SCN(-) (o) (substituted for Cl(-)) was sufficient to inhibit vasomotion. Oscillations in tone, membrane potential, and [Ca(2+)](i) disappeared with 36mM SCN(-). DIDS and Zn(2+) blocked I (Cl(Ca,cGMP)) but not I (Cl(Ca)). Vasomotion was not sensitive to DIDS and Zn(2+), and DIDS and Zn(2+) induce vasomotion in arteries without endothelium. The vasomotion in the presence of DIDS and Zn(2+) was sensitive to 36mM SCN(-) (o). The anion substitution data indicate that Cl(-) is crucial for the V (m) and [Ca(2+)](i) oscillations underlying vasomotion. The Cl(-) channel blocker data are consistent with both CaCCs being important.
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| 5. |
- Brondum, E, et al.
(författare)
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Increased contractility to noradrenaline and normal endothelial function in mesenteric small arteries from the goto-kakizaki rat model of type 2 diabetes.
- 2008
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Ingår i: The journal of physiological sciences : JPS. - 1880-6546. ; 58:5, s. 333-9
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is associated with many circulatory manifestations, including alteration in endothelial function and hypertension. In this study we investigate the morphology and contractile response as well as the endothelial function of resistance arteries from the spontaneously diabetic Goto-Kakizaki (GK) rat, a model of lean type 2 diabetes expressing glucose intolerance. METHODS: Isolated mesenteric small arteries were investigated under isometric conditions in a wire myograph system using noradrenaline (NA) and the endothelium-dependent vasorelaxant acetylcholine (ACh). Media thickness was measured and media lumen ratio calculated. RESULTS: No apparent morphological difference was noted between the arteries from GK rats and control Wistar (CW) rats. When exposed to the maximal NA concentration used (30 microM), arteries from GK rats developed significantly more tension than arteries from CW rats. In the presence of indomethacin (a specific blocker of the COX synthase) and of L-NAME (an inhibitor of eNOS), the response to NA was still significantly greater in GK rat arteries. Under control conditions, arteries from both groups showed intact relaxation to ACh. After incubation with indomethacin and L-NAME, both groups showed a non-NO nonprostaglandin-dependent relaxation to ACh. This relaxation could be blocked by a combination of apamin and charybdotoxin. CONCLUSION: This study shows that mesenteric small arteries from the diabetic GK rat have increased contractile response to NA, along with a normal endothelial function and unaltered morphology.
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| 6. |
- Dige, Irene, et al.
(författare)
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In situ identification of streptococci and other bacteria in initial dental biofilm by confocal laser scanning microscopy and fluorescence in situ hybridization.
- 2007
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Ingår i: European journal of oral sciences. - : Wiley. - 0909-8836 .- 1600-0722. ; 115:6, s. 459-67
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Tidskriftsartikel (refereegranskat)abstract
- Confocal laser scanning microscopy (CLSM) has been employed as a method for studying intact natural biofilm. When combined with fluorescence in situ hybridization (FISH) it is possible to analyze spatial relationships and changes of specific members of microbial populations over time. The aim of this study was to perform a systematic description of the pattern of initial dental biofilm formation by applying 16S rRNA-targeted oligonucleotide probes to the identification of streptococci and other bacteria, and to evaluate the usefulness of the combination of CLSM and FISH for structural studies of bacterial populations in dental biofilm. Biofilms were collected on standardized glass slabs mounted in intra-oral appliances and worn by 10 individuals for 6, 12, 24 or 48 h. After intra-oral exposure the biofilms were labelled with probes against either streptococci (STR405) or all bacteria (EUB338) and analysed by CLSM. The current approach of using FISH techniques enabled differentiation of streptococci from other bacteria and determination of their spatio-temporal organization. The presence of chimney-like multilayered microcolonies with different microbial compositions demonstrated by this methodology provided information supplementary to our previous knowledge obtained by classical electron microscopic methods and increased our understanding of the structure of developing biofilms.
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| 7. |
- Ek, C. Joakim, et al.
(författare)
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Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia
- 2015
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 35:5, s. 818-827
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Tidskriftsartikel (refereegranskat)abstract
- Insults to the developing brain often result in irreparable damage resulting in long-term deficits in motor and cognitive functions. The only treatment today for hypoxic-ischemic encephalopathy (HIE) in newborns is hypothermia, which has limited clinical benefit. We have studied changes to the blood-brain barriers (BBB) as well as regional cerebral blood flow (rCBF) in a neonatal model of HIE to further understand the underlying pathologic mechanisms. Nine-day old mice pups, brain roughly equivalent to the near-term human fetus, were subjected to hypoxia-ischemia. Hypoxia-ischemia increased BBB permeability to small and large molecules within hours after the insult, which normalized in the following days. The opening of the BBB was associated with changes to BBB protein expression whereas gene transcript levels were increased showing direct molecular damage to the BBB but also suggesting compensatory mechanisms. Brain pathology was closely related to reductions in rCBF during the hypoxia as well as the areas with compromised BBB showing that these are intimately linked. The transient opening of the BBB after the insult is likely to contribute to the pathology but at the same time provides an opportunity for therapeutics to better reach the infarcted areas in the brain.
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| 8. |
- Golubinskaya, Veronika, 1974, et al.
(författare)
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Bestrophin-3 Expression in a Subpopulation of Astrocytes in the Neonatal Brain After Hypoxic-Ischemic Injury
- 2019
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Bestrophin-3, a potential candidate for a calcium-activated chloride channel, recently was suggested to have cell-protective functions. We studied the expression and alternative splicing of bestrophin-3 in neonatal mouse brain and after hypoxic-ischemic (HI) injury and in human neonatal brain samples. HI brain injury was induced in 9-day old mice by unilateral permanent common carotid artery occlusion in combination with exposure to 10% oxygen for 50 min. Endoplasmic reticulum stress was induced by thapsigargin treatment in primary culture of mouse brain astrocytes. We also investigated expression of bestrophin-3 protein in a sample of human neonatal brain tissue. Bestrophin-3 protein expression was detected with immunohistochemical methods and western blot; mRNA expression and splicing were analyzed by RT-PCR. HI induced a brain tissue infarct and a pronounced increase in the endoplasmic reticulum-associated marker CHOP. Three days after HI a population of astrocytes co-expressed bestrophin-3 and nestin in a penumbra-like area of the injured hemisphere. However, total levels of Bestrophin-3 protein in mouse cortex were reduced after injury. Mouse astrocytes in primary culture also expressed bestrophin-3 protein, the amount of which was reduced by endoplasmic reticulum stress. Bestrophin-3 protein was detected in astrocytes in the hippocampal region of the human neonatal brain which had patchy white matter gliosis and neuronal loss in the Sommer's sector of the Ammon's horn (CA1). Analysis of bestrophin-3 mRNA in mouse brain with and without injury showed the presence of two truncated spliced variants, but no full-length mRNA. Total amount of bestrophin-3 mRNA increased after HI, but showed only minor injury-related change. However, the splice variants of bestrophin-3 mRNA were differentially regulated after HI depending on the presence of tissue injury. Our results show that bestrophin-3 is expressed in neonatal mouse brain after injury and in the human neonatal brain with pathology. In mouse brain bestrophin-3 protein is upregulated in a specific astrocyte population after injury and is co-expressed with nestin. Splice variants of bestrophin-3 mRNA respond differently to HI, which might indicate their different roles in tissue injury.
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| 9. |
- Golubinskaya, Veronika, 1974, et al.
(författare)
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Bestrophin-3 is differently expressed in normal and injured mouse glomerular podocytes.
- 2015
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Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 214:4, s. 481-496
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Tidskriftsartikel (refereegranskat)abstract
- Bestrophins are putative calcium-activated chloride channels. Recently cell-protective functions for Bestrophin-3 (Best3) were proposed. Best3 exists in different splice variants. We have here examined expression, alternative splicing and localization of Best3 in mouse podocytes under normal conditions and during endoplasmic reticulum (ER) stress.
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| 10. |
- Golubinskaya, Veronika, 1974, et al.
(författare)
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Endothelial Function in a Mouse Model of Myeloperoxidase Deficiency
- 2014
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Ingår i: Biomed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141. ; 2014:128046
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Tidskriftsartikel (refereegranskat)abstract
- Myeloperoxidase (MPO) activity is suggested to reduce the function of vascular nitric oxide, thereby contributing to endothelial dysfunction, although data in rodents are inconclusive. We examined vascular contractile and relaxant responses in MPO-deficient (MPO-/-) and wild- type mice to investigate the role for myeloperoxidase in the development of endothelial dysfunction. Carotid and saphenous arteries were taken from 8-month-old mice and studied in a myograph. Responses of carotid arteries to phenylephrine, high potassium, or acetylcholine (Ach) were statistically not different from controls. Treatment with lipopolysaccharide (LPS; to enhance endothelial dysfunction) reduced responses to Ach in MPO-/- but did not affect responses in wild-type. In response to high concentrations of Ach, carotid arteries responded with transient contractions, which were not different between the groups and not affected by LPS treatment. Saphenous arteries from MPO-/- had smaller normalized diameters and developed less contractile force. Vessels from MPO-/- were less sensitive to Ach than controls. These data suggest that mature MPO-deficient mice do not show enhanced endothelial function compared to wild-type mice, even when provoked with LPS treatment. The EDHF response appears to be reduced in MPO deficiency.
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