Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid

2001 ◽  
Vol 281 (4) ◽  
pp. H1469-H1475 ◽  
Author(s):  
Chunxiang Zhang ◽  
Rakesh Patel ◽  
Jason P. Eiserich ◽  
Fen Zhou ◽  
Stacey Kelpke ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Hypochlorous Acid ◽  
Tissue Injury ◽  
Calcium Ionophore ◽  
Aortic Ring ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Sprague Dawley ◽  
Inflammatory Conditions

The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl) plays a role in tissue injury under inflammatory conditions. The present study tests the hypothesis that HOCl decreases nitric oxide (NO) bioavailability in the vasculature of Sprague-Dawley rats. Aortic ring segments were pretreated with HOCl (1–50 μM) followed by extensive washing. Endothelium-dependent relaxation was then assessed by cumulative addition of acetylcholine (ACh) or the calcium ionophore A23187 . HOCl treatment significantly impaired both ACh- and A23187 -mediated relaxation. In contrast, endothelium-independent relaxation induced by sodium nitroprusside was unaffected. The inhibitory effect of HOCl on ACh-induced relaxation was reversed by exposure of ring segments to l-arginine but notd-arginine. In cellular studies, HOCl did not alter endothelial NO synthase (NOS III) protein or activity, but inhibited formation of the NO metabolites nitrate (NO[Formula: see text]) and nitrite (NO[Formula: see text]). The reduction in total NO metabolite production in bovine aortic endothelial cells was also reversed by addition of l-arginine. These data suggest that HOCl induces endothelial dysfunction via modification ofl-arginine.

Effects of glucocorticoids on prostaglandin formation by human amnion

1990 ◽  
Vol 68 (6) ◽  
pp. 671-676 ◽  
Author(s):  
William Gibb ◽  
Jean-Claude Lavoie
Keyword(s):  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Isolated Cells ◽  
Stimulatory Action ◽  
Human Amnion ◽  
Human Labor ◽  
Epidermal Growth

The human amnion may be an important source of prostaglandins involved in the onset of human labor and therefore it is important to define the factors that regulate their formation in this tissue. In the present study we demonstrate that glucocorticoids inhibit prostaglandin production by freshly isolated amnion cells. The inhibitory action of the glucocorticoids, however, changes to a stimulatory action when the cells are maintained in primary culture for a few days. For both inhibition and stimulation, concentrations of 10−8 M dexamethasone or greater were required to give significant effects, and estradiol and progesterone had no effect on the prostaglandin output of the cells. Epidermal growth factor (EGF), which has previously been found to stimulate prostaglandin output by confluent amnion cells, did not alter prostaglandin output of cells initially placed in culture. Furthermore, the stimulatory action of EGF and dexamethasone appeared additive. The calcium ionophore A23187 stimulated prostaglandin output in freshly isolated cells and accentuated the inhibitory effect of dexamethasone. These studies indicate that prostaglandin formation by human amnion during pregnancy could be regulated by glucocorticoids. These steroids are easily available to the amnion by way of cortisone conversion to Cortisol by the maternal decidua. The results also indicate that amnion is capable of responding to glucocorticoids in both a stimulatory and inhibitory fashion and whether one or both actions are of importance in vivo is a question that is as yet unresolved.Key words: prostaglandins, amnion, fetal membranes, glucocorticoids, labor, pregnancy.

Segmental heterogeneity of NO-mediated pulmonary vasodilation in rats

1994 ◽  
Vol 267 (2) ◽  
pp. H494-H499 ◽  
Author(s):  
M. R. Eichinger ◽  
B. R. Walker
Keyword(s):  
Sodium Nitroprusside ◽  
Arginine Vasopressin ◽  
Calcium Ionophore ◽  
Vascular Occlusion ◽  
Physiological Saline ◽  
Calcium Ionophore A23187 ◽  
Pulmonary Vasculature ◽  
Ionophore A23187 ◽  
Sprague Dawley ◽  
No Donor

Nitric oxide (NO) is known to elicit vasodilation in the preconstricted rat lung. However, the sites of dilation within the pulmonary vasculature remain unknown. We hypothesized that donated NO would dilate all areas of constriction within the pulmonary vasculature, whereas receptor-mediated, NO-induced dilations would correspond to regional binding of agents. Isolated lungs from male Sprague-Dawley rats were perfused at constant flow with physiological saline solution. Pulmonary arterial and pulmonary venous pressures were monitored, while pulmonary microvascular pressures were estimated by vascular occlusion. Lungs were constricted with U-46619, and upon development of a stable degree of vasoconstriction, the NO donor sodium nitroprusside or the endothelium-dependent dilators A23187, arginine vasopressin, or ATP were administered. U-46619 caused constriction of both arterial and venous segments. Administration of sodium nitroprusside and the calcium ionophore A23187 elicited similar dilation of preconstricted arterial and venous segments. Arginine vasopressin significantly dilated both arterial and venous segments, with a greater reversal of venous resistance. In contrast, ATP significantly reduced arterial resistance more than venous. These results demonstrate that donated NO uniformly dilates all constricted regions of the pulmonary vasculature. However, receptor-mediated, endothelium-dependent dilators display characteristic heterogeneities in the sites of decreased pulmonary vascular resistance.

Singlet oxygen scavengers affect laser-dye impairment of endothelium-dependent responses of brain arterioles

1996 ◽  
Vol 270 (4) ◽  
pp. H1258-H1263 ◽  
Author(s):  
W. I. Rosenblum ◽  
G. H. Nelson
Keyword(s):  
Singlet Oxygen ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Protective Effects ◽  
Laser Dye ◽  
Oxygen Scavengers ◽  
Heat Injury

This study investigates the possible role of singlet oxygen in accounting for the inhibitory effect of laser-dye injury on endothelium-dependent dilations. The combination of helium-neon (HeNe) laser (20-s exposure) and intravascular Evans blue impairs endothelium-dependent dilation of mouse pial arterioles by acetylcholine (ACh), bradykinin (BK), and calcium ionophore A23187. Each has a different endothelium-derived mediator (EDRFACh, EDRFBK, EDRFionophore, respectively). In this study, diameters at a craniotomy site were monitored in vivo with an image splitter-television microscope. The laser-dye injury, as usual, abolished the responses 10 and 30 min after injury, with recovery, complete or partial, at 60 min. Dilations by sodium nitroprusside, an endothelium-independent dilator, were not affected by laser-dye. When the singlet oxygen scavengers L-histidine (10(-3) M) and L-tryptophan (10(-2) M) were added to the suffusate over the site, the responses to ACh at 10 and 30 min were relatively intact, the response to BK was partly protected at 10 min only, and the response to ionophore was still totally impaired at 10 and 30 min. Lysine, a nonscavenging amino acid, had no protective effects with any dilator. We postulate that a heat-induced injury initiates a chain of events resulting in prolonged singlet oxygen generation by the endothelial cell (not by the dye). We postulate further that destruction of EDRFACh by singlet oxygen is responsible for laser-dye inhibition of ACh and that generation of the radical must continue for > or = 30 min. On the other hand, the heat injury itself is probably responsible for the elimination of the response to ionophore. Heat plus singlet oxygen generated by heat-damaged tissue may initially impair the response to BK, but by 30 min only the effects of some other factor, presumably heat injury, account for the impaired response to BK.

Calcium modulates vasopressin effect in rabbit cortical collecting tubule

1987 ◽  
Vol 252 (1) ◽  
pp. F115-F121 ◽  
Author(s):  
M. A. Dillingham ◽  
B. S. Dixon ◽  
R. J. Anderson
Keyword(s):  
Calcium Uptake ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Calcium Activity ◽  
Cellular Calcium ◽  
Collecting Tubules ◽  
Bathing Fluid

The calcium ion has been proposed to be an important mediator of the hydroosmotic response to arginine vasopressin (AVP). We examined the effect of reducing basolateral calcium activity on hydraulic conductivity (Lp) in response to AVP in rabbit cortical collecting tubules (CCT) perfused in vitro. Each tubule served as its own control. Reducing bathing fluid calcium from 0.94 mM to 4.6 microM reduced Lp in each tubule (mean decrease from 146 +/- 13 to 106 +/- 7 cm X s-1 X atm X 10(-7), n = 11, P less than 0.025). To determine whether this inhibitory effect was due to a decrease in cellular calcium uptake, we measured the effect of adding 10(-4) M lanthanum to bathing fluid on AVP-stimulated Lp. Lanthanum decreased Lp (from 109 +/- 13 to 80 +/- 10 cm X s-1 X atm X 10(-7), P less than 0.05) in each tubule. To examine the site at which low peritubular calcium activity regulates AVP action, we measured the effect of decreasing bathing fluid calcium on 8-[p-chlorophenylthio]-adenosine 3',5'-cyclic monophosphate (ClPheS-cAMP)-stimulated Lp (n = 5). Decreasing bathing fluid calcium significantly decreases (P less than 0.025) Lp response to ClPheS-cAMP. Since these results suggest that cellular calcium uptake can exert a post-cAMP effect to modulate AVP action, we examined the effect of the calcium ionophore A23187 (10(-7) M) on AVP- and ClPheS-cAMP-stimulated Lp A23187 reversibly potentiates (25-30%, P less than 0.025) the Lp response to both AVP and ClPheS-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory effects of calcium ionophore pretreatment of porcine oocytes on polyspermic fertilization

Zygote ◽  
2006 ◽  
Vol 14 (1) ◽  
pp. 17-22 ◽  
Author(s):  
T. Hayashi ◽  
H. Sato ◽  
H. Iwata ◽  
T. Kuwayama ◽  
Y. Monji
Keyword(s):  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
The Other ◽  
Ionophore A23187 ◽  
Inhibitory Effects ◽  
High Concentration ◽  
Maturation Period ◽  
Low Concentration ◽  
Other Hand

The present study examined the inhibitory effects of various pretreatment concentrations (0–100 μM) of the calcium ionophore A23187 on polyspermic fertilization and then examined the effect of the maturation period and the time between calcium ionophore treatment and fertilization on the inhibitory effect of calcium ionophore on polyspermic fertilization. In experiment 1, a high concentration of calcium ionophore (100 μM) increased the rate of activated oocytes, but the rate of fertilization declined. On the other hand, when oocytes were treated with a low concentration of calcium ionophore (10 μM), monospermic fertilization was significantly increased (10 μM; 31.3%) (p < 0.05). In experiment 2, oocytes were cultured for various times (0, 0.5, 3, 6 h) after calcium ionophore treatment (10 μM) before fertilization. The highest rate of monospermic fertilization was detected in the oocytes cultured for 6 h after calcium ionophore treatment before fertilization. In experiments 3 and 4, we examined the effect of the maturation period (40 h or 44 h) on the rate of fertilization and blastulation of oocytes pretreated with calcium ionophore. The treatment of oocytes with calcium ionophore significantly decreased the rate of polyspermic fertilization regardless of the maturation period (44 h: with calcium ionophore 26.25% vs without 78.8%; 40 h: with calcium ionophore 37.5% vs without 77.5%); however, calcium ionophore treatment increased the rates of monospermic fertilization and blastulation of the oocytes matured for 44 h, but not those matured for 40 h. In conclusion, activation with a low concentration of calcium ionophore (10 μM) and a further 6 h of culture before fertilization improved the rate of monospermic fertilization and blastulation.

scholarly journals Inhibitory effect of LY 255283 on the synthesis of leukotriene B4and thromboxane A2in human peripheral blood polymorphonuclear leukocytes and monocytes

1993 ◽  
Vol 2 (6) ◽  
pp. 407-409 ◽  
Author(s):  
M. Ugur ◽  
M. Melli
Keyword(s):  
Receptor Antagonist ◽  
Peripheral Blood ◽  
Polymorphonuclear Leukocytes ◽  
Human Peripheral Blood ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Human Monocytes

LY 255283 [(1-(5-ethyl-2-hydroxy-4-(6-methyl-6-)1H-tetrazol-5-yl)-heptyloxy) phenyl)ethanone], a specific leukotriene B4(LTB4) receptor antagonist, inhibited the production of LTB4in human peripheral blood polymorphonuclear leukocytes (PMNL) and in monocytes activated by calcium ionophore A23187. In human monocytes activated by ionophore it inhibited also the production of thromboxane B2(TXB2). The effect of LY 255283 on 5-lipoxygenase (5-LO) and LTA4hydrolase activities which catalyse the production of LTB4and LTA4has not been studied yet. It is thought that LY 255283 may inhibit the production of LTB4and TXA2by antagonising the effect of ionophore-induced LTB4on 5-lipoxygenase and cyclooxygenase in human peripheral blood PMNL and monocytes.

Heparin inhibits histamine release from canine mast cells

1993 ◽  
Vol 264 (4) ◽  
pp. L387-L390 ◽  
Author(s):  
N. Inase ◽  
R. E. Schreck ◽  
S. C. Lazarus
Keyword(s):  
Mast Cells ◽  
Charge Density ◽  
Histamine Release ◽  
Negative Charge ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Similar Inhibitory Effect ◽  
Negative Charge Density

To determine the role of heparin in mast cell exocytosis, we studied the effect of heparin on histamine release induced by compound 48/80 or calcium ionophore A23187 in canine mastocytoma cells (BR). Heparin caused concentration-dependent inhibition of compound 48/80-induced histamine release from mast cells (n = 4; P < 0.05) with a mean inhibitory concentration of 0.14 +/- 0.01 U/ml (mean +/- SE). Mean maximal inhibition was 69.3 +/- 2.0%. In contrast, heparin had no effect on calcium ionophore A23187-induced histamine release. Although benzyl alcohol, a preservative of pharmaceutical heparin, had no effect, purified heparin produced a similar inhibitory effect on compound 48/80-induced histamine release (n = 4; P < 0.05). The inhibitory effect of heparin on histamine release was rapid and was eliminated by washing cells. Dextran sulfate, a polysaccharide with negative charge density, produced a similar inhibitory effect on compound 48/80-induced histamine release (n = 4; P < 0.05). We conclude that heparin inhibits compound 48/80-induced exocytosis in mast cells probably by its negative charge density.

Cytopathogenicity of Entamoeba histolytica

1984 ◽  
Vol 307 (1131) ◽  
pp. 73-85 ◽  
Keyword(s):  
Entamoeba Histolytica ◽  
Tissue Injury ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Aetiological Factor ◽  
Ionophore A23187 ◽  
Surface Lipid ◽  
Dense Particle ◽  
Surface Labelling ◽  
Host Cell Membranes

The lesions induced in man by Entamoeba histolytica are characterized by massive tissue injury in the absence of major local signs of a host immune response. The amoeba damages surrounding cells preferentially by contact-mediated cytolysis. Recently, a presumptive aetiological factor underlying this process has been identified. It is a protein, amoebapore, capable of spontaneous incorporation into host cell membranes. Therein it induces high conductance ion-channels which rapidly collapse the cellular transmembrane potential and lead to a prelytic state. Amoebapore is present within the amoeba in a highly aggregated state in a small, dense particle. It is shed into the medium in a particulate form by a stimulus-mediated process. Release is enhanced by addition of concanavalin A, lipopolysaccharide or the calcium ionophore A23187. Surface-labelling of intact amoeba, followed by fractionation of the homogenate in self-generating Percoll gradients, identified two labelled fractions, the plasma membrane and a particulate fraction sedimenting in the region of intracellular particulate amoebapore. This latter fraction appears to be material in the process of exocytosis. A highly immunogenic surface lipid has been identified and shown to be involved in the rapid surface redistribution of immune complexes, their shedding and endocytosis. The relevance of these findings to the immunoprophylaxis of amoebiasis is discussed.

Chronically Impaired Endothelial Vasoreactivity Following Oversized Endovascular Introducer Sheath Placement in Porcine Iliac Arteries: Implications for Endovascular Therapy

Vascular ◽  
2006 ◽  
Vol 14 (6) ◽  
pp. 353-361 ◽  
Author(s):  
Peter H. Lin ◽  
James L. Steinberg ◽  
Tamuru Okada ◽  
Wei Zhou ◽  
Hosam F. El Sayed ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Time Course ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Control Group ◽  
Ionophore A23187 ◽  
Introducer Sheath ◽  
Iliac Arteries ◽  
Endovascular Prosthesis

The conventional endovascular aortic aneurysm procedure entails the placement of oversized introducer sheaths in relatively normal ileofemoral arteries to allow the delivery and deployment of endovascular prosthesis. Endoluminal manipulation with passage of oversized endoluminal devices can lead to endothelial denudation, resulting in impaired cellular function. The purpose of this study was to assess the time course of endothelial function with vasoreactivity following oversized endovascular sheath insertion ranging from 1 day to 16 weeks in normal porcine iliac arteries. Following oversized introducer sheath placement in bilateral iliac arteries, vasoreactivity was tested using both endothelium-dependent and -independent vasodilators. Intravascular ultrasonography showed a significant reduction in the luminal area at 12 and 16 weeks. This was similarly supported by morphometric analysis, which showed increased medial thickness with an elevated intima to media ratio at the same time course. Endothelium-dependent relaxation to bradykinin, calcium ionophore A23187, serotonin, and adenosine diphosphate all uniformly displayed attenuated endothelial dysfunction at all time points when compared with the control group. In contrast, endothelium-independent relaxation showed a decreased vasoresponsiveness at 4 weeks. In conclusion, this study underscored the detrimental and chronic endothelial dysfunction in a normal artery caused by oversized introducer sheath placement. Chronically impaired endothelial function may play a role leading to iliofemoral artery thrombosis or late occlusion, which were well-recognized adverse events following endovascular aneurysm procedures. Our study underscores the importance of appropriate patient selection to minimize potential sheath oversize and endograft device miniaturization to avoid vessel wall injury and maintain vasoreactivity.

Inhibitory Effect of Fentanyl on Acetylcholine-induced Relaxation in Rat Aorta

2004 ◽  
Vol 101 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Ju-Tae Sohn ◽  
Seong-Ho Ok ◽  
Hee-Jin Kim ◽  
Seon-Hak Moon ◽  
Il-Woo Shin ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Response Curve ◽  
Calcium Ionophore ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Acetylcholine Concentration ◽  
Concentration Response Curve

Background Previous study has shown that fentanyl attenuates acetylcholine-induced vasorelaxation. The goal of the current in vitro study was to identify the muscarinic receptor subtype that is mainly involved in the fentanyl-induced attenuation of endothelium-dependent relaxation elicited by acetylcholine. Methods The effects of fentanyl and muscarinic receptor antagonists on the acetylcholine concentration-response curve were assessed in aortic vascular smooth muscle ring preparations precontracted with phenylephrine. In the rings pretreated independently with pirenzepine, 4-diphenylacetoxyl-N-methylpiperidine methiodide, and naloxone, acetylcholine concentration-response curves were generated in the presence and absence of fentanyl. The effect of fentanyl on the concentration-response curve for calcium ionophore A23187 was assessed. Results Fentanyl (0.297 x 10 0.785 x 10 m) attenuated acetylcholine-induced vasorelaxation in ring preparations with or without 10 m naloxone. Pirenzepine (10 to 10 m) and 4-diphenylacetoxyl-N-methylpiperidine methiodide (10 to 10 m) produced a parallel rightward shift in the acetylcholine concentration-response curve. The concentrations (-log M) of pirenzepine and 4-diphenylacetoxyl-N-methylpiperidine methiodide necessary to displace the concentration-response curve of an acetylcholine by twofold were estimated to be 6.886 +/- 0.070 and 9.256 +/- 0.087, respectively. Methoctramine, 10 m, did not alter the acetylcholine concentration-response curve. Fentanyl, 0.785 x 10 m, attenuated acetylcholine-induced vasorelaxation in the rings pretreated with 10 m pirenzepine but had no effect on vasorelaxation in the rings pretreated with 10 m 4-diphenylacetoxyl-N-methylpiperidine methiodide. Fentanyl, 0.785 x 10 m, did not significantly alter calcium ionophore A23187-induced vasorelaxation. Conclusions These results indicate that fentanyl attenuates acetylcholine-induced vasorelaxation via an inhibitory effect at a level proximal to nitric oxide synthase activation on the pathway involving endothelial M3 muscarinic receptor activation in rat aorta.

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