scholarly journals Vasodilatory Effect of Guanxinning Tablet on Rabbit Thoracic Aorta is Modulated by Both Endothelium-Dependent and -Independent Mechanism

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun Ling ◽  
Jiajun Shi ◽  
Quanxin Ma ◽  
Qinqin Yang ◽  
Yili Rong ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Thoracic Aorta ◽  
Calcium Ion ◽  
Calcium Release ◽  
Vascular Tissue ◽  
Salvia Miltiorrhiza ◽  
No Synthase ◽  
Dependent Manner ◽  
Guanxinning Tablet ◽  
Dose Dependent

Vasodilatory therapy plays an important role in the treatment of cardiovascular diseases, especially hypertension and coronary heart disease. Previous research found that Guanxinning tablet (GXNT), a traditional Chinese compound preparation composed of Salvia miltiorrhiza (Danshen) and Ligusticum chuanxiong (Chuanxiong), increase blood flow in the arteries, but whether vasodilation plays a role in this effect remains unclear. Here, we found that GXNT significantly alleviated the vasoconstriction of isolated rabbit thoracic aorta induced by phenylephrine (PE), norepinephrine (NE), and KCl in a dose-dependent manner with or without endothelial cells (ECs). Changes in calcium ion levels in vascular smooth muscle cells (VSMCs) showed that both intracellular calcium release and extracellular calcium influx through receptor-dependent calcium channel (ROC) declined with GXNT treatment. Experiments to examine potassium channels suggested that endothelium-denuded vessels were also regulated by calcium-activated potassium channels (Kca) and ATP-related potassium channels (KATP) but not voltage-gated potassium channels (kv) and inward rectifying potassium channels (KIR). For endothelium-intact vessels, the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) contents in vascular tissue obviously increased after GXNT treatment, and pretreatment with the NO synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) or guanylyl cyclase inhibitor methylthionine chloride (MB) significantly inhibited vasodilation. An assessment of NO-related pathway protein expression revealed that GXNT enhanced the expression of phosphorylated endothelial NO synthase (eNOS) in a dose-dependent manner but had no effect on total eNOS, p-Akt, Akt, or PI3K levels in human umbilical vein ECs (HUVECs). In addition to PI3K/AKT signaling, Ca2+/calmodulin (CaM)-Ca2+/CaM-dependent protein kinase II (CaMKII) signaling is a major signal transduction pathway involved in eNOS activation in ECs. Further results showed that free calcium ion levels were decreased in HUVECs with GXNT treatment, accompanied by an increase in p-CaMKII expression, implying an increase in the Ca2+/CaM-Ca2+/CaMKII cascade. Taken together, these findings suggest that the GXNT may have exerted their vasodilative effect by activating the endothelial CaMKII/eNOS signaling pathway in endothelium-intact rings and calcium-related ion channels in endothelium-denuded vessels.

The calcium antagonist diltiazem inhibits calcification enhanced by calcitonin in growth cartilage of rats in ethane-1-hydroxy-1,1-diphosphonate (EHDP)-induced rickets

1986 ◽  
Vol 113 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Masao Eguchi ◽  
Kenichiro Shibata ◽  
Fumio Wada ◽  
Hideya Kawamura ◽  
Takashi Shimauchi ◽  
...  
Keyword(s):  
Calcium Antagonist ◽  
Calcium Ion ◽  
Concomitant Administration ◽  
Proximal Region ◽  
Dependent Manner ◽  
Short Term ◽  
X Ray ◽  
Growth Cartilage ◽  
Term Administration ◽  
Dose Dependent

Abstract. In an animal model of human rickets developed by giving a short-term administration of large doses of EHDP to young rats, concomitant administration of [Asu1,7]eel calcitonin (CT) with EHDP resulted in the promotion of calcification in growth cartilage. In an attempt to clarify the mechanisms related to the accelerated calcification due to CT, the effects of diltiazem, a calcium antagonist, were studied. Diltiazem suppressed, in a dose-dependent manner, the accelerated calcification due to CT in the growth cartilage, as determined by findings on the soft X-ray photos, contact microradiograph and light microscopic histology of the proximal region of the tibia. This suppression was only evident when diltiazem and CT were given concomitantly. If it is assumed that diltiazem inhibits the entry of calcium ion into the cells of growth cartilage, in the same manner as seen in case of smooth muscle and myocardial cells, then our results indicate that intracellular concentrations of calcium might play an important role in the occurrence of accelerated calcification due to CT.

Abstract 272: Sex Differences in β-Adrenergic Responsiveness of Excitation-Contraction Coupling in Isolated Rabbit Hearts

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Gregory Hoeker ◽  
Ashleigh Hood ◽  
Rodolphe Katra ◽  
Steven Poelzing ◽  
Steven Pogwizd
Keyword(s):  
Sex Differences ◽  
Action Potentials ◽  
Adrenergic Receptor ◽  
Calcium Release ◽  
Dependent Manner ◽  
Ectopic Activity ◽  
Dose Threshold ◽  
Ectopic Beats ◽  
Cardioprotective Effects ◽  
Dose Dependent

Introduction: Sex differences in β-adrenergic receptor (β-AR) responsiveness are associated with female cardioprotection. We hypothesize that female (F) rabbits have reduced responsiveness to β-AR stimulation vs males (M), and that the degree and type of sex differences vary with the β-AR subtypes that are activated. Methods: Ventricular action potentials (AP) and intracellular calcium transients (CaT) were optically mapped from the epicardial surface of rabbit hearts during 3 Hz pacing. Spontaneous calcium release (SCR) and ectopic activity were elicited at 1, 3, and 5.5 Hz. β-responsiveness was assessed with the nonselective β-agonist isoproterenol (Iso, 1-316 nM), or β2-AR selective agonist zinterol (Zin, 10 nM). Results: At baseline, the time constant of CaT decay (τ) was faster in F than M (54.0±1.7 vs 62.1±3.0 ms; n=14, 14; p < 0.05), with no sex difference in CaT duration (CaD80). AP duration (APD90) was shorter in F than M (202.5±5.0 vs 218.2±5.7 ms; p < 0.05). Iso decreased τ, CaD80, and APD90 in a dose-dependent manner in both sexes (n = 5, 5 for F, M). Iso decreased τ to a lesser extent in F than M for 1 and 32-316 nM Iso (F = 11-32 ms, M = 23-48 ms; p < 0.05). The Iso-induced decrease in CaD80 was not significantly different in F than M at any dose. The Iso-induced decrease in APD90 was significantly less in F than M only at 316 nM Iso (75.5±8.7 ms vs 103.9±6.2 ms, p < 0.05). In contrast, there were no sex differences in the response to Zin for τ, CaD80, or APD90 (n = 6, 6 for F, M). Zin decreased τ by 7.2±2.0 ms in F vs 12.7±3.7 ms in M; CaD80 by 18.0±5.3% in F vs 21.1±8.0 ms in M; and APD90 by 24.9±8.5 ms in F vs 21.9±8.9 ms in M. SCR was observed in 50% (6/12) of hearts treated with Zin, whereas Iso elicited SCR in all hearts (10/10) with a dose threshold of 32 nM. No ectopic beats were observed with Zin (0/36 trials in 12 hearts). With Iso, ectopic activity was less frequent in F hearts (16%, 12/75 trials in 5 hearts) than in M hearts (41%, 26/68 trials in 5 hearts, p < 0.05). Conclusions: These results suggest that sex differences in AP and CaT depend on the dose of the agonist used and the β-AR subtypes that are activated. Elucidating nuances of sex differences in β-AR subtype physiology will provide a better understanding of the mechanisms of reduced β-responsiveness in F and its cardioprotective effects.

Interleukin-1β induces nitric oxide production by a mouse pituitary tumour cell line (AtT20/D16)

1993 ◽  
Vol 138 (3) ◽  
pp. 429-435 ◽  
Author(s):  
K. Ohta ◽  
Y. Hirata ◽  
T. Imai ◽  
F. Marumo
Keyword(s):  
Cell Line ◽  
Tumour Cell ◽  
Pituitary Tumour ◽  
No Synthase ◽  
Tumour Cell Line ◽  
Dependent Manner ◽  
Mouse Pituitary ◽  
Dose Dependent ◽  
Inducible Nos ◽  
Acth Release

ABSTRACT To elucidate whether anterior pituitary cells express the nitric oxide (NO) synthase gene, we studied the synthesis of NO and the expression of NO synthase (NOS) mRNA by a mouse pituitary tumour cell line (AtT20/D16). Interleukin-1β (IL-1β) stimulated production of NO2−/NO3− (NOx) in a time-dependent manner and both NOx and cyclic GMP formation were stimulated in a dose-dependent manner by IL-1β. IL-1β-induced NOx production and intracellular cyclic GMP formation were similarly blocked by an NO synthase inhibitor, NG-monomethyl-l-arginine (LNMMA), whose effect was reversed by l-arginine, but not by d-arginine. Dexamethasone inhibited IL-1β-induced NOx production in a dose-dependent manner. A calmodulin inhibitor (W-7) showed no effect on IL-1β-induced NOx production, whereas cycloheximide and the actinomycin D completely inhibited NOx production. Northern blot analysis using cDNA for mouse macrophage-inducible NOS as a probe revealed the expression of inducible NOS mRNA in the cells only after exposure to IL-1β. Although IL-1β stimulated ACTH release from tumour cells, LNMMA failed to affect ACTH release stimulated by IL-1β. These results demonstrate for the first time that a pituitary tumour cell line (AtT20/D16) possesses cytokine-inducible and Ca2+/calmodulin-independent NOS, although NO may not be involved in ACTH release. Journal of Endocrinology (1993) 138, 429–435

Effects of forskolin on bone in organ culture

1987 ◽  
Vol 252 (1) ◽  
pp. E44-E48
Author(s):  
N. S. Krieger ◽  
P. H. Stern
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Calcium Release ◽  
Dependent Manner ◽  
Bone Culture ◽  
Length Of Treatment ◽  
Fetal Rat ◽  
Neonatal Mouse Calvaria ◽  
Dose Dependent

The effects of forskolin, which directly activates adenylate cyclase in most systems, have been compared with the actions of parathyroid hormone and calcitonin, both of which have been suggested to utilize cAMP as a second messenger in their actions on bone. Forskolin alone stimulated calcium release from neonatal mouse calvaria and fetal rat limb bones in vitro in a dose-dependent manner. The effect was maximal at 10(-6) M in both systems. At higher concentrations forskolin completely inhibited stimulated bone resorption, although with submaximal concentrations the inhibition was only partially sustained up to 72 h. Forskolin directly stimulated cAMP release from calvaria into the medium at concentrations up to 10(-4) M. Forskolin had no effect on the interaction between parathyroid hormone and calcitonin, while calcitonin inhibited the stimulatory effect of forskolin comparably with its inhibition of parathyroid hormone-stimulated bone resorption. The results indicate that forskolin has dual effects on bone and can mimic responses of both parathyroid hormone and calcitonin in both bone culture systems. The observed response depends on the concentration of forskolin used and the length of treatment with the drug.

scholarly journals Levobupivacaine differentially suppresses platelet aggregation by modulating calcium release in a dose-dependent manner

2012 ◽  
Vol 50 (3) ◽  
pp. 112-121 ◽  
Author(s):  
Jiin-Tarng Liou ◽  
Chih-Chieh Mao ◽  
Fu-Chao Liu ◽  
Huan-Tang Lin ◽  
Li-Man Hung ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Calcium Release ◽  
Dependent Manner ◽  
Dose Dependent

scholarly journals Regulation of ATP-induced calcium release in COS-7 cells by calcineurin

2000 ◽  
Vol 348 (1) ◽  
pp. 173-181 ◽  
Author(s):  
Arun BANDYOPADHYAY ◽  
Dong-Wook SHIN ◽  
Do Han KIM
Keyword(s):  
Mammalian Cells ◽  
Calcium Release ◽  
Calcineurin Inhibitors ◽  
Dependent Manner ◽  
Transfected Cells ◽  
High Level ◽  
Dose Dependent ◽  
Constitutively Active

Experiments were conducted to examine the role of calcineurin in regulating Ca2+ fluxes in mammalian cells. In COS-7 cells, increasing concentrations (1-10 μM) of ATP triggered intracellular Ca2+ release in a dose-dependent manner. Treatment of the cells with calcineurin inhibitors such as cyclosporin A (CsA), deltamethrin and FK506 resulted in an enhancement of ATP-induced intracellular Ca2+ release. Measurement of calcineurin-specific phosphatase activity in vitro demonstrated a high level of endogenous calcineurin activities in COS-7 cells, which was effectively inhibited by the addition of deltamethrin or CsA. The expression of constitutively active calcineurin (CnA∆CaMAI) inhibited the ATP-induced increase in intracellular Ca2+ concentration ([Ca2+]i), in both the presence and the absence of extracellular Ca2+. These results suggest that the constitutively active calcineurin prevented Ca2+ release from the intracellular stores. In the calcineurin-transfected cells, treatment with CsA restored the calcineurin-mediated inhibition of intracellular Ca2+ release. Protein kinase C-mediated phosphorylation of Ins(1,4,5)P3 receptor [Ins(1,4,5)P3R] was partly inhibited by the extracts prepared from the vector-transfected cells and completely inhibited by those from cells co-transfected with CnA∆CaMAI and calcineurin B. On the addition of 10 μM CsA, the inhibited phosphorylation of Ins(1,4,5)P3R was restored in both the vector-transfected cells and the calcineurin-transfected cells. These results show direct evidence that Ca2+ release through Ins(1,4,5)P3R in COS-7 cells is regulated by calcineurin-mediated dephosphorylation.

The role of intracellular Ca2+ during early sexual development in Dictyostelium discoideum: effects of LaCl3, LaCl3, Ins(1,4,5)P3, TMB-8, chlortetracycline and A23187 on cell fusion

1988 ◽  
Vol 90 (3) ◽  
pp. 465-473 ◽  
Author(s):  
MICHAEL A. LYDAN ◽  
DANTON H. O'DAY
Keyword(s):  
Dictyostelium Discoideum ◽  
Cell Fusion ◽  
Calcium Release ◽  
Cytosolic Calcium ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Extracellular Environment ◽  
Internal Calcium

The agents LaCl3, Ins(1,4,5)P3, TMB-8, chlortetracycline (CTC) and A23187 were used to study the requirement for internal calcium mobilization during gamete cell fusion in Dictyostelium discoideum. The inhibition of the influx of calcium (LaCl3) prevented cell fusion in a dose-dependent manner. At the intracellular level, Ins(1,4,5)P3, an endogenous regulator of calcium release from intracellular stores, stimulated cell fusion within one hour following its addition. Treatment with agents that prevent the release of calcium from intracellular stores (TMB-8, CTC) also inhibited cell fusion in a dose-dependent manner. However, the non-specific augmentation of cytosolic calcium levels through the use of the ionophore A23187 inhibited cell fusion, and the amount inhibition was directly related to the drug concentration. Studies on cell morphology and growth plus results from reversibility experiments involving the ability to form macrocysts reveal that these effects are not due to non-specific drug toxicity. In total, these results suggest that the mobilization of calcium both from the extracellular environment and from intracellular stores important and is probably regulated during gamete cell fusion in D. discoideum.

scholarly journals Comparative Contractile Effects of Halothane and Sevoflurane in Rat Aorta

2000 ◽  
Vol 92 (1) ◽  
pp. 219-219 ◽  
Author(s):  
Vu Huu Vinh ◽  
Taijiro Enoki ◽  
Shinichi Hirata ◽  
Hiroshi Toda ◽  
Masahiro Kakuyama ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Thoracic Aorta ◽  
Volatile Anesthetic ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Dependent Manner ◽  
Anesthetic Agents ◽  
Rat Thoracic Aorta ◽  
Dose Dependent ◽  
Ca2 Channels

Background Volatile anesthetic agents have been shown to have contractile effects in vascular tissues during specific conditions. This study compared contractile effects of halothane and sevoflurane in rat aorta treated with verapamil. This study also tried to elucidate the mechanism of the contraction. Methods Endothelium-denuded rat thoracic aorta was used for recording of isometric tension and measurement of influx of 45Ca2+. All experiments were performed in the presence of verapamil. In recording of tension, rings were precontracted with a submaximum dose of phenylephrine, followed by exposure to halothane or sevoflurane. For measurement of influx of 45Ca2+, rat aortic strips were exposed to phenylephrine and then to additional halothane or sevoflurane. Influx of Ca2+ was estimated by incubating the strips in 45Ca2+-labeled solution for 2 min. Results Halothane (0.5-4.0%) induced contraction in a dose-dependent manner, whereas sevoflurane (1-4%) had no effect on tension. Influx of 45Ca2+ was strongly enhanced by halothane at 1% and 2%, but only slightly at 4%, and was not affected by 1-4% sevoflurane. SK&F 96365, a blocker of voltage-independent Ca2+ channels, abolished contraction and influx of 45Ca2+ by 1% halothane. Depletion of Ca2+ from the sarcoplasmic reticulum with ryanodine or thapsigargin reduced the contraction induced by halothane at 4% but not that at 1% and 2%. Conclusion Halothane is suggested to cause contraction by enhancing influx of Ca2+ via voltage-independent Ca2+ channels at concentrations up to 2% and by inducing release of Ca2+ at 4%. Sevoflurane (1-4%) is devoid of these contractile effects.

scholarly journals Nitric Oxide is Produced by Cowdria ruminantium-Infected Bovine Pulmonary Endothelial Cells In Vitro and Is Stimulated by Gamma Interferon

1998 ◽  
Vol 66 (5) ◽  
pp. 2115-2121 ◽  
Author(s):  
Mbithe Mutunga ◽  
Patricia M. Preston ◽  
Keith J. Sumption
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
No Synthase ◽  
No Production ◽  
Dependent Manner ◽  
Donor Molecule ◽  
No Donor ◽  
Pulmonary Endothelial Cells ◽  
Cowdria Ruminantium ◽  
Dose Dependent

ABSTRACT Nitric oxide (NO) is a labile inorganic free radical produced by NO synthase from the substrate l-arginine in various cells and tissues including endothelial cells. A substantial elevation of nitrite levels indicative of NO production occurred in cultures ofCowdria ruminantium-infected bovine pulmonary endothelial cells (BPEC) incubated in medium alone. Exposure of the infected cultures to recombinant bovine gamma interferon (BorIFN-γ) resulted in more rapid production of NO, reduced viability of C. ruminantium, and induction of endothelial cell death. Significant inhibition of NO production was noted after addition of the NO synthase inhibitor N-monomethyl-l-arginine (l-NMMA), indicating that the increase in production occurred via the inducible NO synthase pathway. Reduction in the infectivity of C. ruminantium elementary bodies (EBs) occurred in a dose-dependent manner after incubation with the NO donor moleculeS-nitroso-N-acetyl-dl-penicillamine (SNAP) prior to infection of endothelial cells. The level of infection in cultures maintained in SNAP was reduced in a dose-dependent manner with significant negative correlation between the final level of infection on day 7 and the level of SNAP (r = −0.96). It was established that pretreatment and cultivation of C. ruminantium EBs with the NO donor molecule SNAP reduced infectivity to cultures and viability of EBs with the implication that release of NO in vivo following infection of endothelial cells may have an effect upon the multiplication of the agent in the host animal and may be involved in the pathogenesis of heartwater through the effect of this molecule upon circulation.

Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue

1997 ◽  
Vol 272 (5) ◽  
pp. L823-L829 ◽  
Author(s):  
E. K. Birks ◽  
M. Bousamra ◽  
K. Presberg ◽  
J. A. Marsh ◽  
R. M. Effros ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Vascular Tissue ◽  
Pulmonary Arteries ◽  
Arachidonic Acid Metabolite ◽  
Dependent Manner ◽  
Western Blots ◽  
Human Lungs ◽  
Pulmonary Arterial ◽  
Endogenous Modulators ◽  
Dose Dependent

We investigated the effect of 20-hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid metabolite of the cytochrome P-450 (cP450) 4A pathway, on human pulmonary arterial tone. 20-HETE elicited a dose-dependent and indomethacin-inhibitable vasodilation of isolated small pulmonary arteries. Whole lung microsomes metabolized [24C]arachidonic acid into 20-HETE and a variety of leukotrienes, epoxyeicosatrienoic acids, and prostanoids. Indomethacin blocked formation of prostanoids without effects on the conversion of arachidonate into 20-HETE, 20-HETE was converted by lung microsomes into prostanoids, raising the possibility that 20-HETE may be metabolized by cyclooxygenase enzymes in vascular tissue to a vasodilatory compound. Western blots probed with a polyclonal antibody to cP450 4A identified a protein of approximately 50 kDa immunologically similar to the cP450 4A in rat liver. We conclude that small arteries from human lungs dilate upon exposure to 20-HETE in a cyclooxygenase-dependent manner and that the proteins and enzymatic activity required to synthesize this product are present in lungs. Our observations suggest that cP450 enzyme products could be endogenous modulators of pulmonary vascular tone.

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