scholarly journals Do Mistletoe (Viscum album L.) Lectins Influence Isometric Contraction of Non-diseased Human Mesenteric Arteries ex vivo?

2021 ◽  
Vol 25 (1) ◽  
pp. 41-52
Author(s):  
Daniela Dimitrova ◽  
◽  
Biliana Nikolova ◽  
Vanya Bogoeva ◽  
Bozhil Robev ◽  
...  
Keyword(s):  
Contractile Response ◽  
Ex Vivo ◽  
Viscum Album ◽  
Smooth Muscle Contraction ◽  
Mesenteric Arteries ◽  
Isometric Contractions ◽  
Plant Lectins ◽  
High K ◽  
Basal Tone ◽  
Vascular Smooth Muscle Contraction

Mistletoe (Viscum album L., VA) lectins (MLs) are plant lectins with potent anticancer activity. Although wide use of VA extracts in curing cancer, the effects of purified MLs on human vasculature in term of possible side effect of the lectin has not yet been reported. The present study was aimed to investigate isometric contractions of isolated human mesenteric arteries during MLs application. The contractile response of arteries was studied using Mulvany-Halpern myograph and the isometric contractions under MLs’ treatment were examined in artery segments with either intact endothelium or after endothelium removal. Furthermore, the effect of the lectin was assessed in arterial preparations in basal tension, in arteries precontracted with 42 mM KCl as a depolarizing stimulus or endothelin-1 (ET-1) as a potent receptor-operated agonist of vascular smooth muscle contraction. The results showed that MLs (1 to 100 nM) failed to affect the high K+-induced contractions of both endothelium-intact and endothelium-denuded arteries. The contractions of tissue preparations without endothelium in basal tone or after ET-1 (1 nM) treatment were also not affected by the application of MLs. The observed mild effect of MLs on the contractility of human vasculature may potentially be beneficial with MLs-based anticancer therapy without vascular side effects.

Abstract 509: Essential Role of Vascular Smooth Muscle Bmal1 in Diurnal Variations of Contraction and Blood Pressure

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Wen Su ◽  
Zhongwen Xie ◽  
Zhenheng Guo ◽  
Ming C Gong
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Essential Role ◽  
Smooth Muscle Contraction ◽  
Diurnal Variations ◽  
Mesenteric Arteries ◽  
Isometric Contractions ◽  
Vascular Smooth Muscle Contraction

Bmal1 is an obligatory core clock gene that is ubiquitously expressed but has been demonstrated to have tissue specific functions. However, the vascular smooth muscle specific function of bmal1 is unknown. We generated a smooth muscle specific bmal1 knockout mouse model (SM-bmal1-ko) and investigated the role of bmal1 in vascular smooth muscle contraction and blood pressure regulation. Isometric contractions were measured in isolated right renal artery and 2 nd order branch of mesenteric artery helical strips. Blood pressure was monitored in conscious free-moving mice using radiotelemetry. We demonstrated that bmal1 was selectively deleted in smooth muscle enriched tissues like mesenteric arteries. Moreover, the diurnal variations of bmal1 target genes per1/2 were abolished in mesenteric arteries. The isometric contractions in response to alpha1 agonist phenylephrine and to 5-HT were significantly diminished in vascular helical strips isolated from SM-bmal1-ko mice compared to that from control flox mice. The contractile diurnal variations detected in the renal arteries isolated from control flox mice were significantly diminished in samples isolated from SM-bmal1-ko mice. Moreover, in vivo , the diurnal variations in the instantaneous pressor responses to intravenous phenylephrine injection were significantly diminished in SM-bmal1-ko mice compared to control flox mice. Twenty four hour mean arterial blood pressure was significantly decreased under 12:12 light:dark, constant light or constant dark conditions. Importantly, the amplitude of blood pressure diurnal variations was significantly diminished in SM-bmal1-ko mice. Importantly, neither the level nor the diurnal variations of locomotor activity was affected by bmal1 deletion. This indicates that the central SCN clock function is not affected in the SM-bmal1-ko mice and the blood pressure alterations in SM-bmal1-ko mice is not a consequence of changed locomotor activity. Taken together, our results demonstrate an essential role of bmal1 in the diurnal variations of vascular smooth muscle contraction and blood pressure.

Norepinephrine and endothelin activate diacylglycerol kinases in caveolae/rafts of rat mesenteric arteries: agonist-specific role of PI3-kinase

2007 ◽  
Vol 292 (5) ◽  
pp. H2248-H2256 ◽  
Author(s):  
Christopher J. Clarke ◽  
Vasken Ohanian ◽  
Jacqueline Ohanian
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Contraction ◽  
Smooth Muscle Contraction ◽  
Pi3 Kinase ◽  
Mesenteric Arteries ◽  
Dependent Manner ◽  
Kinase Inhibition ◽  
Small Arteries ◽  
Vascular Smooth Muscle Contraction

The phosphatidylinositol (PI) signaling pathway mediates norepinephrine (NE)- and endothelin-1 (ET-1)-stimulated vascular smooth muscle contraction through an inositol-trisphosphate-induced rise in intracellular calcium and diacylglycerol (DG) activation of protein kinase C (PKC). Subsequent activation of DG kinases (DGKs) metabolizes DG to phosphatidic acid (PA), potentially regulating PKC activity. Because precise regulation and spatial restriction of the PI pathway is necessary for specificity, we have investigated whether this occurs within caveolae/rafts, specialized plasma membrane microdomains implicated in vascular smooth muscle contraction. We show that components of the PI signaling cascade-phosphatidylinositol 4,5-bisphosphate (PIP2), PA, and DGK-θ are present in caveolae/rafts prepared from rat mesenteric small arteries. Stimulation with NE or ET-1 induced [33P]PIP2 hydrolysis solely within caveolae/rafts. NE stimulated an increase in DGK activity in caveolae/rafts alone, whereas ET-1 activated DGK in caveolae/rafts and noncaveolae/rafts; however, [33P]PA increased in all fractions with both agonists. Previously, we reported that NE activated DGK-θ in a phosphatidylinositol 3-kinase (PI3-kinase)-dependent manner; here, we describe PI3-kinase-dependent DGK activation and [33P]PA production in caveolae/rafts in response to NE but not ET-1. Additionally, PKB, a potential activator of DGK-θ, translocated to caveolae/rafts in response to NE but not ET-1, and PI3-kinase inhibition prevented this. Furthermore, PI3-kinase inhibition reduced the sensitivity of contraction to NE but not ET-1. Our study shows that caveolae/rafts are major sites of vasoconstrictor hormone activation of the PI pathway in intact small arteries and suggest a link between lipid signaling events within caveolae/rafts and contraction.

Contractions of the canine coronary artery in calcium-free solution

1984 ◽  
Vol 247 (2) ◽  
pp. H259-H263
Author(s):  
T. W. Rooke ◽  
T. J. Rimele ◽  
P. M. Vanhoutte
Keyword(s):  
Coronary Artery ◽  
Contractile Response ◽  
Potassium Concentration ◽  
Smooth Muscle Contraction ◽  
Free Solution ◽  
High Potassium ◽  
Prostaglandin F2 Alpha ◽  
Canine Saphenous Vein ◽  
Canine Coronary Artery ◽  
Vascular Smooth Muscle Contraction

Prostaglandin F2 alpha, but not norepinephrine, augments the maximal contractile response to potassium. To examine the mechanism underlying this augmentation, rings of canine coronary artery were studied isometrically in physiological salt solutions of various composition. The contractions evoked by prostaglandin F2 alpha were larger in high-potassium, calcium-free solution than in calcium-free solution. Similar results were obtained using canine saphenous vein and femoral artery. Isoproterenol, but not nimodipine, relaxed the contractions produced by prostaglandin F2 alpha in high-potassium, calcium-free solution. Unlike prostaglandin F2 alpha, norepinephrine failed to constrict rings in high-potassium, calcium-free solution. In calcium-free solution, prostaglandin F2 alpha-induced contractions increased with increasing potassium concentrations, but no enhancement occurred when lithium was substituted for potassium. Rings of coronary artery incubated with calcium-45 did not show changes in prostaglandin F2 alpha-induced calcium-45 efflux following changes in potassium concentration. These results suggest that potassium enhances coronary vascular smooth muscle contraction to prostaglandin F2 alpha, but not norepinephrine, independently of calcium entry.

scholarly journals NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 147
Author(s):  
Romuald Brice Babou Kammoe ◽  
Gilles Kauffenstein ◽  
Julie Pelletier ◽  
Bernard Robaye ◽  
Jean Sévigny
Keyword(s):  
Smooth Muscle ◽  
Ex Vivo ◽  
Smooth Muscle Contraction ◽  
Receptor Activation ◽  
Nucleoside Triphosphate ◽  
Nucleotide Receptors ◽  
Nerve Terminals ◽  
Wild Type ◽  
Nucleoside Triphosphate Diphosphohydrolase ◽  
Bladder Contraction

Nucleotides released by smooth muscle cells (SMCs) and by innervating nerve terminals activate specific P2 receptors and modulate bladder contraction. We hypothesized that cell surface enzymes regulate SMC contraction in mice bladder by controlling the concentration of nucleotides. We showed by immunohistochemistry, enzymatic histochemistry, and biochemical activities that nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and ecto-5′-nucleotidase were the major ectonucleotidases expressed by SMCs in the bladder. RT-qPCR revealed that, among the nucleotide receptors, there was higher expression of P2X1, P2Y1, and P2Y6 receptors. Ex vivo, nucleotides induced a more potent contraction of bladder strips isolated from NTPDase1 deficient (Entpd1−/−) mice compared to wild type controls. The strongest responses were obtained with uridine 5′-triphosphate (UTP) and uridine 5′-diphosphate (UDP), suggesting the involvement of P2Y6 receptors, which was confirmed with P2ry6−/− bladder strips. Interestingly, this response was reduced in female bladders. Our results also suggest the participation of P2X1, P2Y2 and/or P2Y4, and P2Y12 in these contractions. A reduced response to the thromboxane analogue U46619 was also observed in wild type, Entpd1−/−, and P2ry6−/− female bladders showing another difference due to sex. In summary, NTPDase1 modulates the activation of nucleotide receptors in mouse bladder SMCs, and contractions induced by P2Y6 receptor activation were weaker in female bladders.

scholarly journals Reduced biomechanical models for precision-cut lung-slice stretching experiments

2021 ◽  
Vol 82 (5) ◽  
Author(s):  
Hannah J. Pybus ◽  
Amanda L. Tatler ◽  
Lowell T. Edgar ◽  
Reuben D. O’Dea ◽  
Bindi S. Brook
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Ex Vivo ◽  
Finite Thickness ◽  
Biomechanical Model ◽  
Local Stress ◽  
Smooth Muscle Contraction ◽  
Biomechanical Models ◽  
Cytokine Activation ◽  
Asymptotic Reduction

AbstractPrecision-cut lung-slices (PCLS), in which viable airways embedded within lung parenchyma are stretched or induced to contract, are a widely used ex vivo assay to investigate bronchoconstriction and, more recently, mechanical activation of pro-remodelling cytokines in asthmatic airways. We develop a nonlinear fibre-reinforced biomechanical model accounting for smooth muscle contraction and extracellular matrix strain-stiffening. Through numerical simulation, we describe the stresses and contractile responses of an airway within a PCLS of finite thickness, exposing the importance of smooth muscle contraction on the local stress state within the airway. We then consider two simplifying limits of the model (a membrane representation and an asymptotic reduction in the thin-PCLS-limit), that permit analytical progress. Comparison against numerical solution of the full problem shows that the asymptotic reduction successfully captures the key elements of the full model behaviour. The more tractable reduced model that we develop is suitable to be employed in investigations to elucidate the time-dependent feedback mechanisms linking airway mechanics and cytokine activation in asthma.

α-Adrenoceptor agonists and the Ca2+-dependence of smooth muscle contraction: evidence for subtypes of receptors or for agonist-dependent differences in the agonist-receptor interaction?

1985 ◽  
Vol 68 (s10) ◽  
pp. 55s-63s ◽  
Author(s):  
John C. McGrath
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Continuous Spectrum ◽  
Contractile Response ◽  
Nitrilotriacetic Acid ◽  
Smooth Muscle Contraction ◽  
Receptor Type ◽  
Receptor Interaction ◽  
Initial Transient ◽  
Adrenoceptor Agonists

1. The effects of varying [Ca2+]o on the contraction of smooth muscle by different α-adrenoceptor agonists were examined on rat isolated anococcygeus muscle. Agonists were tested in the presence of various [Ca2+]o or ‘Ca2+-re-addition curves’ were constructed. In some experiments the [Ca2+]free was buffered with EGTA and nitrilotriacetic acid. The components of the response which were revealed were further analysed by using drugs which modify Ca2+ mobilization. 2. Three separate elements in the contractile response were identified: (i) an initial transient contraction, due to intracellular Ca2+ release could be isolated with [Ca2+]o between 1 nmol/l and 3 μmol/l (this could be obtained only with noradrenaline, phenylephrine and amidephrine); (ii) a nifedipine-sensitive response requiring [Ca2+]o of 3 μmol/l or more; (iii) a nifedipine-resistant response requiring [Ca2+]o of 100 μmol/l or more. Presumably (ii) and (iii) involve the entry of Ca2+o: they could be obtained with all agonists tested, including these above, methoxamine, indanidine and xylazine. 3. The results are discussed in relation to the possibility of distinct types of response and their relationship to subgroups of receptors or agonists. It is concluded that there is a continuous spectrum of activity across the agonist range and that this is likely to correlate with ‘efficacy’ at a single α1 receptor type.

Modulation of arterial Na+-K+-ATPase-induced [Ca2+]i reduction and relaxation by norepinephrine, ET-1, and PMA

1999 ◽  
Vol 276 (2) ◽  
pp. H651-H657 ◽  
Author(s):  
Francisco Pérez-Vizcaíno ◽  
Angel Cogolludo ◽  
Juan Tamargo
Keyword(s):  
Enzyme Activity ◽  
Smooth Muscle ◽  
Membrane Potential ◽  
Atpase Activity ◽  
Vascular Tone ◽  
Smooth Muscle Contraction ◽  
Mesenteric Arteries ◽  
Free Solution ◽  
Kinase C ◽  
Protein Kinase C Inhibitor

Na+-K+-ATPase plays a major role in regulating membrane potential and vascular tone. We analyzed the modulation by norepinephrine (NE), endothelin-1 (ET-1), and phorbol 12-myristate 13-acetate (PMA) of Na+-K+-ATPase-induced cytoplasmic free Ca2+concentration ([Ca2+]i) reduction and relaxation in isolated endothelium-denuded piglet mesenteric arteries. KCl (0.2–8.8 mM)-induced [Ca2+]ireduction and relaxation in arteries incubated in K+-free solution were used as functional indicators of Na+-K+-ATPase activity. KCl-induced relaxations after exposure to K+-free solution were associated with a reduction in [Ca2+]i, as measured by fura 2 fluorescence. However, KCl reduced [Ca2+]ibelow resting values, whereas force was reduced to near resting values. NE, ET-1, and PMA inhibited the relaxant effects of KCl, and this effect was attenuated by the protein kinase C inhibitor staurosporine but not by the phospholipase A2inhibitor quinacrine. However, ET-1 and PMA potentiated the [Ca2+]i-reducing effect of KCl. In conclusion, ET-1, PMA, and NE are functional inhibitors of Na+-K+-ATPase activity in endothelium-denuded piglet mesenteric arteries, even when the direct effect on the enzyme activity may be stimulatory rather than inhibitory. This can be explained because ET-1, PMA, and NE induce Ca2+ sensitization for smooth muscle contraction, and therefore relaxations do not parallel the reductions in [Ca2+]iafter the activation of Na+-K+-ATPase.

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