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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 1067 (1991), S. 191-200 
    ISSN: 0005-2736
    Keywords: ATPase, (Ca^2^+Mg^2^+)- ; Ectoenzyme ; Nucleoside triphosphatase ; Small artery
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 1067 (1991), S. 201-207 
    ISSN: 0005-2736
    Keywords: ATPase, (Ca^2^+Mg^2^+)- ; Ectoenzyme ; Nucleoside triphosphatase ; Small artery
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 189 (1992), S. 1620-1623 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2013
    Keywords: Key words Weak acid ; Smooth muscle ; pH ; Osmolarity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In vitro both acetate and hyperosmolarity cause vasodilation, which could be physiologically important during food ingestion and during peritoneal dialysis. The purpose of this study was to investigate the role of the intracellular calcium concentration ([Ca2+]i, measured with fura-2), membrane potential (measured with glass microelectrodes) and intracellular pH [pHi, measured with bis-carboxyethylcarboxyfluorescein (BCECF)] in the vasodilation. Hyperosmolar sodium acetate (30 mM) concentration dependently relaxed noradrenaline-precontracted arteries. This response was associated with hyperpolarization and a fall in [Ca2+]i. In arteries precontracted with 50 mM K+ the relaxation was associated with a decrease of [Ca2+]i but no change in membrane potential. Isoosmolar sodium acetate neither relaxed or affect [Ca2+]i of K+-precontracted arteries, but induced a small relaxation with no reduction in [Ca2+]i in noradrenaline-precontracted arteries. Hyperosmolar acetate caused a transient reduction of pHi that was unrelated to relaxation. It is concluded that the mechanisms responsible for the relaxation to hyperosmolar acetate involve a decrease of [Ca2+]i, which is only partly explained by hyperpolarization and probably a decrease in the sensitivity of the contractile proteins to [Ca2+]i. pHi seems not to play a role in these effects.
    Type of Medium: Electronic Resource
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  • 5
    Publication Date: 2015-10-17
    Description: Major depression is known to be associated with cardiovascular abnormalities, and oxidative stress has been suggested to play a role. We tested the hypothesis that antidepressant treatment reduces oxidative stress and endothelial dysfunctions in the chronic mild stress (CMS) model of depression in rats. Rats with 〉30% reduction in sucrose intake after 4 wk of CMS were defined in the study as CMS-susceptible and compared with unstressed controls. Sixteen CMS-susceptible and eight unstressed rats were treated during weeks 5 to 8 of the CMS protocol with escitalopram. Escitalopram-treated rats with 〉20% recovery in the sucrose consumption during the last 2 wk of treatment were defined as escitalopram responders. Rats that did not reach these criteria were defined as escitalopram nonresponders. In the open field test, escitalopram responders demonstrated anxiolytic effect of treatment. In mesenteric small arteries, escitalopram affected neither NO nor cyclooxygenase-1 (COX-1)-mediated vasodilation. Escitalopram potentiated endothelium-dependent hyperpolarization-like response, which was suppressed in the vehicle-treated CMS-susceptible rats and reduced COX-2-dependent relaxation, which was elevated in the vehicle-treated CMS-susceptible rats. Escitalopram did not affect blood pressure and heart rate, which were elevated in the vehicle-treated CMS-susceptible rats. Oxidative stress markers were changed in association with CMS in liver, heart, and brain. Escitalopram normalized oxidative stress markers in the majority of tissues. This study demonstrates that the antidepressant effect of escitalopram is associated with partial improvement of endothelial function in small arteries affecting COX-2 and endothelium-dependent hyperpolarization-like pathways.
    Print ISSN: 0363-6119
    Electronic ISSN: 1522-1490
    Topics: Medicine
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  • 6
    Publication Date: 2016-11-03
    Description: We investigated the acute effects of glucagon-like peptide-1 (GLP-1), GLP-1(1–36), and GLP-1(7–36) on vascular endothelial growth factor-A (VEGFA)-induced endothelium-dependent signaling and vasodilation. Our hypothesis was that GLP-1 released from intestinal l -cells modulates processes related to PLC activation, Src, and endothelial NOS (eNOS) signaling, thereby controlling endothelial vessel tone. By using RT-PCR analysis, we found mRNA for the GLP-1 receptor (GLP-1R) in human dermal microvascular endothelial cells (HDMEC), human retinal microvascular endothelial cells, and rat arteries. In isolated rat mesenteric resistance arteries precontracted with the thromboxane analog U46619 to 80–90% of maximum contraction, VEGFA (25 ng/ml) caused a small and gradual relaxation (28.9 ± 3.9%). Pretreatment of arteries with either GLP-1(1–36) (500 nM) or GLP-1(7–36) (1 nM) abolished the VEGFA-induced relaxation. VEGFA-induced relaxations were also inhibited in endothelial-denuded arteries and in arteries pretreated with the nitric oxide synthase (NOS) inhibitor, N-nitro- l -arginine methyl ester (100 μM). In vivo studies on male Wistar rats also revealed that GLP-1(7–36) inhibited VEGFA-induced vasodilation of the same arteries. In isolated endothelial cells, GLP-1(1–36) and GLP-1(7–36) caused a reduction in VEGFA-induced phosphorylation of PLC. Ca 2+ imaging of endothelial cells and rat mesenteric resistance arteries using fura-2, revealed that both GLP-1 analogs caused a reduction in VEGFA-induced Ca 2+ signaling. GLP-1(1–36) also reduced VEGFA-induced eNOS phosphorylation in HDMEC. In conclusion, GLP-1 reduced relaxation induced by VEGFA in resistance arteries by inhibiting VEGFR2-mediated Ca 2+ signaling and endothelial NO synthesis. GLP-1, on its own, also induced phosphorylation of Src and ERK1/2 that can lead to proliferation and is implicated in vessel permeability.
    Keywords: Vascular Biology and Microcirculation
    Print ISSN: 0363-6135
    Electronic ISSN: 1522-1539
    Topics: Medicine
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  • 7
    Publication Date: 2013-11-02
    Description: The high blood pressure in giraffe leg arteries renders giraffes vulnerable to edema. We investigated in 11 giraffes whether large and small arteries in the legs and the tight fascia protect leg capillaries. Ultrasound imaging of foreleg arteries in anesthetized giraffes and ex vivo examination revealed abrupt thickening of the arterial wall and a reduction of its internal diameter just below the elbow. At and distal to this narrowing, the artery constricted spontaneously and in response to norepinephrine and intravascular pressure recordings revealed a dynamic, viscous pressure drop along the artery. Histology of the isolated median artery confirmed dense sympathetic innervation at the narrowing. Structure and contractility of small arteries from muscular beds in the leg and neck were compared. The arteries from the legs demonstrated an increased media thickness-to-lumen diameter ratio, increased media volume, and increased numbers of smooth muscle cells per segment length and furthermore, they contracted more strongly than arteries from the neck (500 ± 49 vs. 318 ± 43 mmHg; n = 6 legs and neck, respectively). Finally, the transient increase in interstitial fluid pressure following injection of saline was 5.5 ± 1.7 times larger ( n = 8) in the leg than in the neck. We conclude that 1 ) tissue compliance in the legs is low; 2 ) large arteries of the legs function as resistance arteries; and 3 ) structural adaptation of small muscle arteries allows them to develop an extraordinary tension. All three findings can contribute to protection of the capillaries in giraffe legs from a high arterial pressure.
    Print ISSN: 0363-6119
    Electronic ISSN: 1522-1490
    Topics: Medicine
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  • 8
    Publication Date: 2012-07-03
    Description: The specific role of different isoforms of the Na,K-pump in the vascular wall is still under debate. We have previously suggested that the α 2 isoform of the Na,K-pump (α 2 ), Na + , Ca 2+ -exchange (NCX), and connexin43 form a regulatory microdomain in smooth muscle cells (SMCs), which controls intercellular communication and contractile properties of the vascular wall. We have tested this hypothesis by downregulating α 2 in cultured SMCs and in small arteries with siRNA in vivo. Intercellular communication was assessed by using membrane capacitance measurements. Arteries transfected in vivo were tested for isometric and isobaric force development in vitro; [Ca 2+ ] i was measured simultaneously. Cultured rat SMCs were well-coupled electrically, but 10 μM ouabain uncoupled them. Downregulation of α 2 reduced electrical coupling between SMCs and made them insensitive to ouabain. Downregulation of α 2 in small arteries was accompanied with significant reduction in NCX expression. Acetylcholine-induced relaxation was not different between the groups, but the endothelium-dependent hyperpolarizing factor-like component of the response was significantly diminished in α 2 -downregulated arteries. Micromolar ouabain reduced in a concentration-dependent manner the amplitude of norepinephrine (NE)-induced vasomotion. Sixty percent of the α 2 -downregulated arteries did not have vasomotion, and vasomotion in the remaining 40% was ouabain insensitive. Although ouabain increased the sensitivity to NE in the control arteries, it had no effect on α 2 -downregulated arteries. In the presence of a low NE concentration the α 2 -downregulated arteries had higher [Ca 2+ ] i and tone. However, the NE EC50 was reduced under isometric conditions, and maximal contraction was reduced under isometric and isobaric conditions. The latter was caused by a reduced Ca 2+ -sensitivity. The α 2 -downregulated arteries also had reduced contraction to vasopressin, whereas the contractile response to high K + was not affected. Our results demonstrate the importance of α 2 for intercellular coupling in the vascular wall and its involvement in the regulation of vascular tone.
    Print ISSN: 0363-6135
    Electronic ISSN: 1522-1539
    Topics: Medicine
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  • 9
    Publication Date: 2014-07-02
    Description: In smooth muscle cells, K + permeability is high, and this highly influences the resting membrane potential. Lymph propulsion is dependent on phasic contractions generated by smooth muscle cells of lymphatic vessels, and it is likely that K + channels play a critical role in regulating contractility in this tissue. The aim of this study was to investigate the contribution of distinct K + channels to human lymphatic vessel contractility. Thoracic ducts were harvested from 43 patients and mounted in a wire myograph for isometric force measurements or membrane potential recordings with an intracellular microelectrode. Using K + channel blockers and activators, we demonstrate a functional contribution to human lymphatic vessel contractility from all the major classes of K + channels [ATP-sensitive K + (K ATP ), Ca 2+ -activated K + , inward rectifier K + , and voltage-dependent K + channels], and this was confirmed at the mRNA level. Contraction amplitude, frequency, and baseline tension were altered depending on which channel was blocked or activated. Microelectrode impalements of lymphatic vessels determined an average resting membrane potential of –43.1 ± 3.7 mV. We observed that membrane potential changes of 〈5 mV could have large functional effects with contraction frequencies increasing threefold. In general, K ATP channels appeared to be constitutively open since incubation with glibenclamide increased contraction frequency in spontaneously active vessels and depolarized and initiated contractions in previously quiescent vessels. The largest change in membrane voltage was observed with the K ATP opener pinacidil, which caused 24 ± 3 mV hyperpolarization. We conclude that K + channels are important modulators of human lymphatic contractility.
    Print ISSN: 0363-6135
    Electronic ISSN: 1522-1539
    Topics: Medicine
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  • 10
    Publication Date: 2014-01-16
    Description: Lymphatic vessels from animals have been shown to be innervated. While morphological studies have confirmed human lymphatic vessels are innervated, functional studies supporting this are lacking. The present study demonstrates a functional innervation of the human thoracic duct (TD) that is predominantly adrenergic. TDs harvested from 51 patients undergoing esophageal and cardia cancer surgery were either fixed for structural investigations or maintained in vitro for the functional assessment of innervation by isometric force measurements and electrical field stimulation (EFS). Electron microscopy and immunohistochemistry suggested scarce diffuse distribution of nerves in the entire vessel wall, but nerve-mediated contractions could be induced with EFS and were sensitive to the muscarinic receptor blocker atropine and the α-adrenoceptor blocker phentolamine. The combination of phentolamine and atropine resulted in a near-complete abolishment of EFS-induced contractions. The presence of sympathetic nerves was further confirmed by contractions induced by the sympathomimetic and catecholamine-releasing agent tyramine. Reactivity to the neurotransmitters norepinephrine, substance P, neuropeptide Y, acetylcholine, and methacholine was demonstrated by exogenous application to human TD ring segments. Norepinephrine provided the most consistent responses, whereas responses to the other agonists varied. We conclude that the human TD is functionally innervated with both cholinergic and adrenergic components, with the latter of the two dominating.
    Print ISSN: 0363-6135
    Electronic ISSN: 1522-1539
    Topics: Medicine
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