| 1. |
- Mulvany, M J, et al.
(författare)
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Potentiating and depressive effects of ouabain and potassium-free solutions on rat mesenteric resistance vessels.
- 1982
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Ingår i: Circulation research. - 0009-7330. ; 51:4, s. 514-24
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the in vitro effects of ouabain and K-free solutions on some pharmacological and electrophysiological properties of rat mesenteric resistance vessels (internal diameter approximately 190 micrometers). Vessels were mounted as ring preparations on a myograph capable of measuring their isometric wall tension. In normal saline solutions, vessels did not exhibit any tone and had a membrane potential of -54 mV. Both 1 mM ouabain and K-free solutions caused a transient depolarization of 5-8 mV; thereafter the membrane slowly depolarized to about -45 mV after 30 minutes. There was no mechanical response to ouabain, but K-free solutions caused a transient development of tension which could be inhibited by phentolamine (1 microM). In norepinephrine-activated vessels, exposure to ouabain or K-free solutions caused a small depolarization and an increase in tension. Long-term (30-minute) exposure to 1 mM ouabain or K-free solutions reduced the amplitude of norepinephrine responses and, for the lower (but not the higher) norepinephrine concentrations, the membranes were about 14 mV more depolarized than control. The mechanical responses to a cocktail of norepinephrine in a high potassium solution were, however, unaffected. Re-exposure to normal saline solution produced a transient hyperpolarization and transiently eliminated the norepinephrine response, but thereafter the membrane potential and response returned to normal. The results indicate that ouabain and K-free solutions can have both short-term potentiating and long-term depressive effects on the mechanical response of rat mesenteric resistance vessels to norepinephrine.
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| 2. |
- Ulleryd, Marcus A, et al.
(författare)
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Stimulation of alpha 7 nicotinic acetylcholine receptor (α7nAChR) inhibits atherosclerosis via immunomodulatory effects on myeloid cells.
- 2019
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 287, s. 122-133
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Tidskriftsartikel (refereegranskat)abstract
- Alpha 7 nicotinic acetylcholine receptor (α7nAChR) stimulation can regulate acute inflammation, and lack of α7nAChR accelerates atherosclerosis in mice. In this study, we aimed to investigate the effects of the novel α7nAChR agonist, AZ6983, on atherosclerosis and assess its possible immunomodulating effects.AZ6983 was tested in vitro in LPS-challenged mouse and human blood and in vivo using the acute inflammatory air pouch model. Thereafter, long-term effects of AZ6983 treatment on atherosclerosis and immune responses were assessed in apoE-/- mice after 8 and 12 weeks. Atherosclerosis was investigated in the aortic root and thoracic aorta, serum levels of cytokines were analysed and RNAseq was used to study aortic gene expression. Further, bone-marrow-derived macrophages were used to assess phagocytosis in vitro.α7nAChR activation by AZ6983 decreased pro-inflammatory cytokines in acute stimulations of human and mouse blood in vitro, as well as in vivo using the air pouch model. Treating apoE-/- mice with AZ6983 decreased atherosclerosis by 37-49% and decreased serum cytokine levels. RNAseq analysis of aortae suggested the involvement of several specific myeloid cell functions, including phagocytosis. In line with this, AZ6983 significantly increased phagocytosis in bone marrow-derived macrophages.This study demonstrates that activation of α7nAChR with AZ6983 inhibits atherosclerosis in apoE-/-mice and that immunomodulating effects on myeloid cells, such as enhanced phagocytosis and suppression of inflammatory cytokines, could be part of the athero-protective mechanisms. The observed anti-inflammatory effect in human blood supports the idea that AZ6983 may decrease disease also in humans.
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| 3. |
- 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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| 4. |
- Lisander, Björn, 1940, et al.
(författare)
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Baroreceptor-induced decrease in muscle blood flow upon propranolol administration.
- 1978
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Ingår i: European journal of pharmacology. - 0014-2999. ; 50:3, s. 275-8
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Tidskriftsartikel (refereegranskat)abstract
- The acute effects of propranolol, 1 mg/kg i.v., were studied in chloralosed, vagotomized cats. The vascularly isolated but innervated calf muscles were perfused from another animal. In one group of experiments, the carotid baroreceptors were exposed to ambient arterial pressure. Here, propranolol caused a fall in heart rate and an increase in resistance of the isolated muscle bed. In other experiments, the carotid sinuses were perfused at a constant pressure. In these animals, no increase in muscle flow resistance was observed after the drug. It is concluded that the increase in total peripheral resistance, seen initially upon propranolol administration, may be reflexly induced via the baroreceptors.
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| 5. |
- Mulvany, M J, et al.
(författare)
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Are isolated femoral resistance vessels or tail arteries good models for the hindquarter vasculature of spontaneously hypertensive rats?
- 1982
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Ingår i: Acta physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 116:3, s. 275-83
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the extent to which the properties of small arteries from the hindquarters of spontaneously hypertensive rats (SHRs) are consistent with the characteristics of perfused SHR hindquarter preparations (for which the relaxed vascular resistance, the reactivity and the sensitivity are reported to be increased). We have therefore compared the in vitro morphological and pharmacological properties of a femoral resistance vessel (i.d. ca 200 microns) and of the tail artery (i.d. ca 600 microns) from SHRs with those from control Wistar-Kyoto rats (WKYs). When relaxed, for any given wall tension, the internal circumference of the SHR resistance vessels was reduced, but that of the SHR tail artery was normal. When activated with 10 microM noradrenaline, the SHR resistance vessels had an increased calcium sensitivity, but the calcium sensitivity of the SHR tail arteries was normal. However, the maximum response of both types of SHR vessels was such that the vessels would have been able to contract against increased transmural pressure. The noradrenaline sensitivity of the SHR resistance vessels was normal but the SHR tail arteries had a decreased sensitivity. The results suggest that the femoral resistance vessel is in general a better model for the hindquarter vasculature than the tail artery.
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| 6. |
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| 7. |
- Mulvany, M J, et al.
(författare)
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Role of membrane potential in the response of rat small mesenteric arteries to exogenous noradrenaline stimulation.
- 1982
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Ingår i: The Journal of physiology. - 0022-3751. ; 332, s. 363-73
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Tidskriftsartikel (refereegranskat)abstract
- 1. We have made simultaneous measurements of membrane potential and wall tension in rat 200 microns mesenteric arteries. 2. The resting membrane potential was -59.2 +/- 0.4 mV and stable (218 measurements, fifty-two vessels). 3. With maximal exogenous noradrenaline stimulation (10 microM) the membrane depolarized to about -34 mV. During the onset of tension development oscillations (period about 6 sec) in both tension and membrane potential were often seen; the membrane potential changes led the tension changes by about 1.2 sec. 4. In the presence of increased K+ (e.g. 40 mM), vessels had an increased noradrenaline sensitivity, and here noradrenaline stimulation produced little change in membrane potential. 5. With maximal K+ stimulation (85 mM), in the presence of phentolamine (1 microM), the membrane depolarized to about -17 mV, the tension being about 70% of the maximal noradrenaline response. 6. In the presence of phentolamine (1 microM), noradrenaline caused hyperpolarization without tension development. The hyperpolarization was inhibited by propranolol and mimicked by isoprenaline. 7. The results suggest that in these small vessels membrane potential variations are not essential to, but have an important modulating influence on, the tension response to exogenous noradrenaline.
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| 8. |
- Nguy, Lisa, 1985, et al.
(författare)
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Vascular function in rats with adenine-induced chronic renal failure.
- 2012
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 1522-1490 .- 0363-6119. ; 302:12
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to characterize the function of resistance arteries, and the aorta, in rats with adenine-induced chronic renal failure (A-CRF). Sprague-Dawley rats were randomized to chow with or without adenine supplementation. After 6-10 wk, mesenteric arteries and thoracic aortas were analyzed ex vivo by wire myography. Plasma creatinine concentrations were elevated twofold at 2 wk, and eight-fold at the time of death in A-CRF animals. Ambulatory systolic and diastolic blood pressures measured by radiotelemetry were significantly elevated in A-CRF animals from week 3 and onward. At death, A-CRF animals had anemia, hyperphosphatemia, hyperparathyroidism, and elevated plasma levels of asymmetric dimethylarginine and oxidative stress markers. There were no significant differences between groups in the sensitivity, or maximal response, to ACh, sodium nitroprusside (SNP), norepinephrine, or phenylephrine in either mesenteric arteries or aortas. However, in A-CRF animals, the rate of aortic relaxation was significantly reduced following washout of KCl (both in intact and endothelium-denuded aorta) and in response to ACh and SNP. Also the rate of contraction in response to KCl was significantly reduced in A-CRF animals both in mesenteric arteries and aortas. The media of A-CRF aortas was thickened and showed focal areas of fragmented elastic lamellae and disorganized smooth muscle cells. No vascular calcifications could be detected. These results indicate that severe renal failure for a duration of less than 10 wk in this model primarily affects the aorta and mainly slows the rate of relaxation.
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| 9. |
- Nilsson, Holger, 1956, et al.
(författare)
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Prolonged exposure to ouabain eliminates the greater norepinephrine-dependent calcium sensitivity of resistance vessels in spontaneously hypertensive rats.
- 1981
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Ingår i: Hypertension (Dallas, Tex. : 1979). - 0194-911X. ; 3:6, s. 691-7
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Tidskriftsartikel (refereegranskat)abstract
- The effects of 30 minutes of exposure to ouabain on calcium sensitivity have been investigated in two types of resistance vessels from 12 pairs of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Branches of the superior mesenteric and femoral arteries, with internal diameters of about 200 micrometer, were mounted as ring preparations in a myograph capable of measuring their isometric wall tension. Dose-response curves for calcium upon norepinephrine stimulation were determined under conditions where neuronal uptake was eliminated. Initially, when stimulated with norepinephrine, the SHR vessels from both locations were more sensitive to calcium and had stronger contractions than their controls. The addition of ouabain (1 mM) to the relaxed vessels immediately elicited a moderate, transient contraction in the branches of the femoral artery, whereas no response was observed in the mesenteric vessels. Although the addition of ouabain to activated vessels produced an immediate potentiation of the response, prolonged (30-minute) exposure to ouabain reduced active tension development upon norepinephrine stimulation in all vessels. The reduction was greatest in the SHR vessels, so that, under these conditions, the norepinephrine-activated calcium sensitivity of corresponding SHR and WKY vessels was similar. By contrast, responses to norepinephrine in high potassium solution were unaffected. The results suggest that under normal conditions, SHR vessels may have a specific increase in the permeability of the norepinephrine-activated calcium channels. Prolonged exposure to ouabain appears to reduce the permeability of these channels, providing an explanation for why this treatment eliminates the difference in calcium sensitivity of the SHR and WKY vessels.
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| 10. |
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