Pregnancy-induced changes in ovine cerebral arteries

1992 ◽  
Vol 262 (1) ◽  
pp. R137-R143 ◽  
Author(s):  
A. D. Hull ◽  
D. M. Long ◽  
L. D. Longo ◽  
W. J. Pearce
Keyword(s):  
Cerebral Arteries ◽  
Calcium Ionophore ◽  
Cellular Protein ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Cross Sectional ◽  
Pregnant Sheep ◽  
Relaxant Response ◽  
Cellular Protein Content ◽  
Induced Changes

We examined the effects of pregnancy on the ovine cerebral vasculature by comparing several characteristics of isolated endothelium-intact segments of three intracranial arteries including the middle cerebral (MCA), posterior communicating (PC), and basilar (BAS) arteries taken from pregnant sheep (138-143 days gestation, term approximately 145 days) and nonpregnant controls. For comparison, segments of the extracranial common carotid (COM) artery were also studied. With pregnancy, vessel water content increased (5.4-5.8%) in all arteries except the PC. Additionally, cellular protein content increased in all arteries (4.4-50.0%). Arterial stiffness, as determined by passive stress-strain determinations, was significantly decreased during pregnancy in the MCA but not in the larger arteries. Maximum contractile responses, when normalized to vessel wall cross-sectional area, were consistently greater in arteries from pregnant than in those from nonpregnant animals (10.1-49.7%). Relaxation to the endothelium-independent guanylate cyclase stimulator S-nitroso-N-acetyl penicillamine (SNAP) increased with pregnancy only in the distal MCA (approximately 17%). Endothelium-dependent relaxation to the calcium ionophore A23187 decreased only in the larger and more proximal COM (-39%). Thus pregnancy was associated with an increase in production of contractile force, a decrease in peripheral vascular stiffness, a decrease in the relaxant response to A23187 in the COM, and an increase in the relaxant response to SNAP in the MCA. Together, these findings indicate that pregnancy has widespread and important vessel specific cerebrovascular consequences that affect not only arterial composition, but also contractility and endothelial reactivity.

Pharmacological studies on relaxation of spastic primate cerebral arteries in subarachnoid hemorrhage

1989 ◽  
Vol 71 (6) ◽  
pp. 909-915 ◽  
Author(s):  
Kenji Kanamaru ◽  
Bryce K. A. Weir ◽  
J. Max Findlay ◽  
Christel A. Krueger ◽  
David A. Cook
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Receptor Antagonist ◽  
Autologous Blood ◽  
Cerebral Arteries ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Small Component ◽  
Content Type ◽  
Prostaglandin F

✓ Chronic cerebral vasospasm was induced in 16 monkeys by direct placement of a clot of autologous blood over the arteries of the circle of Willis on the right side. The middle cerebral arteries (MCA's) on the clot side all showed angiographic vasospasm, which was maximal 7 days after subarachnoid hemorrhage. Animals were sacrificed at this time and vascular responses to acetylcholine (ACh), histamine, and the calcium ionophore A23187 were studied in MCA rings from the clot (spastic) side and the non-clot (control) side. In control preparations with an intact endothelium, which had been precontracted by prostaglandin F2agr; (PGF2agr;), histamine and A23187 produced significant relaxation. The same concentrations of histamine and A23187 did not relax vascular tissues in which the endothelium had been mechanically removed. Acetylcholine did not produce a significant endothelium-dependent relaxation of primate MCA rings, but did relax rings of primate common carotid artery. Pretreatment with chlorpheniramine (an H1-receptor antagonist) prevented histamine-induced relaxation; however, cimetidine (an H2-receptor antagonist) had no inhibitory action. It thus seems that histamine mediates relaxation of intact MCA's mostly by an H1-receptor-mediated release of endothelium-derived relaxing factor (EDRF). Relaxations induced by histamine and A23187 in MCA's from the clot side were substantially reduced. Moreover, the small component of ACh-induced relaxation was also abolished. Endothelium-independent relaxation induced by glyceryl trinitrate (GTN) occurred in arteries from both the control and the clot sides. Constrictions induced by KCl and PGF2agr; were reduced on the clot side of the MCA's. These results suggest that subarachnoid hemorrhage influences both the generation of EDRF and the constriction of affected arteries. The small contraction which was elicited in spastic arteries was fully relaxed by GTN.

Impaired endothelium-mediated relaxation in isolated cerebral arteries from insulin-resistant rats

2002 ◽  
Vol 282 (6) ◽  
pp. H2060-H2065 ◽  
Author(s):  
Benedek Erdös ◽  
Allison W. Miller ◽  
David W. Busija
Keyword(s):  
Vascular Function ◽  
Cerebral Arteries ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Control Mechanisms ◽  
Control Groups ◽  
Insulin Resistant ◽  
Middle Cerebral Arteries ◽  
And Control

Insulin resistance (IR) impairs vascular responses in peripheral arteries. However, the effects of IR on cerebrovascular control mechanisms are completely unexplored. We examined the vascular function of isolated middle cerebral arteries (MCAs) from fructose-fed IR and control rats. Endothelium-dependent vasodilation elicited by bradykinin (BK) was reduced in IR compared with control MCAs. Maximal dilation to BK (10−6 M) was 38 ± 3% ( n = 13) in control and 19 ± 3% ( n = 10) in IR arteries ( P < 0.01). N ω-nitro-l-arginine methyl ester (l-NAME; 10 μM) decreased responses to BK in control arteries by ∼65% and inhibited the already reduced responses completely in IR MCAs. Indomethacin (10 μM) reduced relaxation to BK in control MCAs by ∼40% but was largely ineffective in IR arteries. Combined l-NAME and indomethacin treatments eliminated the BK-induced dilation in both groups. Similarly to BK, endothelium-mediated and mainly cyclooxygenase (COX)-dependent dilation to calcium ionophore A23187 was reduced in IR arteries compared with controls. In contrast, vascular relaxation to sodium nitroprusside was similar between the IR and control groups. These findings demonstrate that endothelium-dependent dilation in cerebral arteries is impaired in IR primarily because of a defect of the COX-mediated pathways. In contrast, nitric oxide-mediated dilation remains intact in IR arteries.

Superoxide anion is an endothelium-derived contracting factor

1989 ◽  
Vol 257 (1) ◽  
pp. H33-H37 ◽  
Author(s):  
Z. S. Katusic ◽  
P. M. Vanhoutte
Keyword(s):  
Superoxide Dismutase ◽  
Xanthine Oxidase ◽  
Superoxide Anion ◽  
Cerebral Arteries ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Heat Inactivation ◽  
Ionophore A23187 ◽  
Excitatory Effect ◽  
Basilar Arteries

The calcium ionophore A23187 causes endothelium-dependent contractions in canine basilar arteries. Removal of the endothelium, or treatment with indomethacin or superoxide dismutase (SOD), prevented the endothelium-dependent excitatory effect of the calcium ionophore. Catalase and deferoxamine were without effect. Superoxide anion generated by xanthine plus xanthine oxidase in the presence of catalase caused contractions of the vascular smooth muscle, which were abolished by SOD or heat inactivation of xanthine oxidase. The A23187-induced production of prostaglandins F2 alpha and E2 and thromboxane B2 was abolished by the removal of endothelium and by treatment with indomethacin but was not affected by the presence of SOD plus catalase. These observations are consistent with the hypothesis that superoxide anion, rather than prostaglandins generated by hydroperoxidase activity of cyclooxygenase, is an endothelium-derived contracting factor in canine cerebral arteries.

The effects of chronic depolarization on L-type 1,4-dihydropyridine-sensitive, voltage-dependent Ca2+ channels in chick neural retina and rat cardiac cells

1991 ◽  
Vol 69 (7) ◽  
pp. 914-920 ◽  
Author(s):  
J. Ferrante ◽  
D. J. Triggle ◽  
A. Rutledge
Keyword(s):  
Calcium Channels ◽  
Calcium Ionophore ◽  
Neural Retina ◽  
Cellular Protein ◽  
Calcium Ionophore A23187 ◽  
Cardiac Cells ◽  
Ionophore A23187 ◽  
Down Regulation ◽  
Voltage Dependent ◽  
Chronic Depolarization

Chick neural retina cells contain functional L-type voltage-dependent Ca2+ channels sensitive to 1,4-dihydropyridines. To investigate the effects of chronic depolarization, cells were grown in medium containing elevated K+. After 4-h to 4-day treatments with elevated K+ (12–73 mM), there was a concentration-dependent decrease in high affinity [3H]PN200-110 binding. Saturation analysis of cells treated for 4 days with 40 mM K+ showed a reduction in maximum ligand binding with no change in affinity. Control and experimental Bmax values were 70.7 ± 6.4 and 42.2 ± 4.5 fmol/mg protein, respectively, and control and experimental KD values were 70.2 ± 7.4 and 68.6 ± 7.4 × 10−12 M. The effect of chronic depolarization was time-dependent, reversible, and without effect on cellular protein content. Reduction in 45Ca2+ uptake following chronic depolarization correlated well with the reduction in [3H]PN200-110 binding. The calcium ionophore A23187, 10−6 M for 24 h, also decreased the binding site density. The calcium channel antagonist D600 had no effect alone on [3H]PN200-110 binding; however, D600 blocked the down-regulation of calcium channels induced by chronic depolarization. The mechanism for Ca2+ channel down-regulation may involve calcium entry, since the effect was blocked by D600 and mimicked by the calcium ionophore A23187. Chronic depolarization with either elevated K+ or veratridine, or chronic treatment with A23187 had no effect on calcium channels in rat neonatal ventricular myocytes, although these cells express functional channels of the 1,4-dihydropyridine-sensitive class. That apparently similar channels in cardiac cells were not affected by chronic depolarization likely indicates structural or regulatory differences between cardiac and neuronal L-type Ca2+ channels.Key words: calcium channels, calcium antagonists, 1,4-dihydropyridines, channel regulation, retinal neurons.

Effects of Ca2+ and furosemide on Cl- transport and O2 uptake in rat parotid acini

1986 ◽  
Vol 251 (2) ◽  
pp. C175-C185 ◽  
Author(s):  
B. Nauntofte ◽  
J. H. Poulsen
Keyword(s):  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
O2 Consumption ◽  
O2 Uptake ◽  
Luminal Membrane ◽  
Cotransport System ◽  
Rat Parotid ◽  
Induced Changes ◽  
Cl Permeability

Stimulation-induced changes in Cl- content and O2 consumption of collagenase-isolated rat parotid acini were measured. In less than 10 s, carbachol caused a net Cl- efflux, corresponding to approximately 50% of the Cl- content, and increased the O2 uptake by 100%. The increase was inhibitable by ouabain and was dependent on the presence of extracellular Ca2+. Furosemide reduced the unstimulated 36Cl- uptake and prevented the reuptake of Cl- after carbachol-induced release. This suggests that a cotransport system is operating in both the unstimulated and stimulated states. Furthermore, furosemide inhibited the stimulated ouabain-sensitive O2 uptake. Raising intracellular Ca2+ by the calcium ionophore A23187 evoked the same pattern of Cl- loss and O2 uptake as carbachol. Our results are compatible with the following hypothesis. Carbachol raises intracellular Ca2+, causing an increased Cl- permeability of the luminal membrane, resulting in a net Cl- efflux. A subsequently enhanced influx of Cl- and Na+ via a furosemide-sensitive cotransport system increases intracellular Na+. This stimulates the Na+-K+-ATPase and thereby the O2 consumption.

Adducin in platelets: activation-induced phosphorylation by PKC and proteolysis by calpain

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2418-2426 ◽  
Author(s):  
Diana M. Gilligan ◽  
Rami Sarid ◽  
Joleen Weese
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
High Speed ◽  
Kinase Inhibitor ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Cytoskeletal Proteins ◽  
Ionophore A23187 ◽  
Capping Protein ◽  
Induced Changes

Adducins are a family of cytoskeletal proteins encoded by 3 genes (alpha, beta, and gamma). Platelets express alpha and gamma adducins, in contrast to red blood cells that express alpha and beta adducins. During platelet activation with thrombin, calcium ionophore A23187, or phorbol 12-myristate 13-acetate, alpha and gamma adducins were phosphorylated by protein kinase C (PKC) as detected by an antibody specific for a phosphopeptide sequence in the highly conserved carboxy terminus. Platelet activation also led to adducin proteolysis; inhibition by calpeptin suggests that the protease was calpain. The kinase inhibitor staurosporine inhibited PKC phosphorylation of adducin and also inhibited proteolysis of adducin. Experiments with recombinant alpha adducin demonstrated that the PKC-phosphorylated form was proteolyzed at a significantly faster rate than the unphosphorylated form. The concentration of adducin in platelets was estimated at 6 μM, similar to the concentration of capping protein. Fractionation of platelets into high-speed supernatant (cytosol) and pellet (membrane and cytoskeleton) revealed a shift of PKC-phosphorylated adducin to the cytosol during platelet activation. Platelet aggregation detected turbidometrically was decreased in the presence of staurosporine and was completely inhibited by calpeptin. Thrombin-induced changes in morphology were assessed by confocal microscopy with fluorescein phalloidin and were not prevented by staurosporine or calpeptin. Our results suggest that regulation of adducin function by PKC and calpain may play a role in platelet aggregation.

Growth factors and the primary cilium in BALB/c 3T3 cells

1987 ◽  
Vol 45 ◽  
pp. 830-831
Author(s):  
R. W. Tucker ◽  
N. S. More ◽  
S. Jayaraman
Keyword(s):  
Growth Factors ◽  
Primary Cilium ◽  
Cultured Cells ◽  
Morphological Changes ◽  
Calcium Ionophore ◽  
Growth Stimulation ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
3T3 Cells ◽  
Microtubule Depolymerization

The mechanisms by which polypeptide growth factors Induce DNA synthesis in cultured cells is not understood, but morphological changes Induced by growth factors have been used as clues to Intracellular messengers responsible for growth stimulation. One such morphological change has been the transient disappearance of the primary cilium, a “9 + 0” cilium formed by the perinuclear centriole in interphase cells. Since calcium ionophore A23187 also produced both mitogenesis and ciliary changes, microtubule depolymerization might explain ciliary disappearance monitored by indirect immunofluorescence with anti-tubulin antibody. However, complete resorption and subsequent reformation of the primary cilium occurs at mitosis, and might also account for ciliary disappearance induced by growth factors. To settle this issue, we investigated the ultrastructure of the primary cilium using serial thin-section electron microscopy of quiescent BALB/c 3T3 cells before and after stimulation with serum.

Inhibition of Platelet Aggregation by Ethanol in Vitro Shows Specificity for Aggregating Agent Used and Is Influenced by Platelet Lipid Composition

1982 ◽  
Vol 48 (01) ◽  
pp. 049-053 ◽  
Author(s):  
C G Fenn ◽  
J M Littleton
Keyword(s):  
Platelet Aggregation ◽  
Lipid Composition ◽  
Saturated Fatty Acids ◽  
Calcium Ionophore ◽  
Cholesterol Content ◽  
Membrane Lipid ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Increased Sensitivity

SummaryEthanol at physiologically tolerable concentrations inhibited platelet aggregation in vitro in a relatively specific way, which may be influenced by platelet membrane lipid composition. Aggregation to collagen, calcium ionophore A23187 and thrombin (low doses) were often markedly inhibited by ethanol, adrenaline and ADP responses were little affected, and aggregation to exogenous arachidonic acid was actually potentiated by ethanol. Aggregation to collagen, thrombin and A23187 was inhibited more by ethanol in platelets enriched with saturated fatty acids than in those enriched with unsaturated fats. Platelets enriched with cholesterol showed increased sensitivity to ADP, arachidonate and adrenaline but this increase in cholesterol content did not appear to influence the inhibition by ethanol of platelet responses. The results suggest that ethanol may inhibit aggregation by an effect on membrane fluidity and/or calcium mobilization resulting in decreased activity of a membrane-bound phospholipase.

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.

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