Effect of Divalent Cations on the Contractile Response of Rat Aorta to Depolarization before and after Nifedipine Treatment

Pharmacology ◽  
1996 ◽  
Vol 53 (2) ◽  
pp. 98-108 ◽  
Author(s):  
M.A. Noguera ◽  
S. Chulia ◽  
M. Elorriaga ◽  
M.D. Ivorra ◽  
P. D’Ocon
Keyword(s):  
Contractile Response ◽  
Divalent Cations ◽  
Rat Aorta ◽  
Before And After

The Effect On Serum-Thromboxan B2 Production, Platelet Aggregation, Serotonin Release, PF-4 And 6-Keto-PGF1αOf A Novel Specific Thromboxan A2 Synthetase-Inhibitor In Patients With Hyperactive Platelets

1981 ◽  
Author(s):  
J B Knudsen ◽  
A Juhl ◽  
J Gormsen
Keyword(s):  
Platelet Aggregation ◽  
Fold Increase ◽  
Rat Aorta ◽  
Serotonin Release ◽  
Human Umbilical Cord ◽  
Synthetase Inhibitor ◽  
Thromboxane Synthetase ◽  
Effective Inhibition ◽  
Before And After ◽  
Acid Hydrochloride

A novel, specific Thromboxan A2-synthetase inhibitor 4-1-2- (1 H-imidazol-l-yl)ethoxy-benzoic acid hydrochloride was given to nine patients with hyperactive platelets (defined by an aggregation threshold 0.05 ug/ml epinepherine) and nine controls. The effects on serum Thromboxan B2, platelet aggregation, serotonin release, PF-4, and 6-keto-PGF1 were evaluated in sequential blood samples from h to 24 h after single dose of loo mg. The serum-thromboxan production measured by RIA was reduced 96% ± 4.3 sd 1/2 h to 2 h after dosing. Platelet+aggregation was reduced 89 ± lo.2% with epinephrine, 92 ± 11.4% with collagen and 56 ± 14.3% with ADP. Serotonin release induced by ADP was reduced 65 ± 9.8%, while PF-4 showed no consistant changes. When crushed rat aorta or microsome preparations from human umbilical cord arteries were incubated with PRP from patients before and after dosing, and aggregation induced by 16 uM ADP, a 6 fold increase in 6-keto PGF1α production measured by RIA was observed. The Ivy-bleeding time was prolonged by 65±14sd %.Conclusion: Specific inhibition of the platelet thromboxane synthetase in patients induces a highly effective inhibition of thromboxane production, and inhibition of platelet aggregability and serotonin release and an increase in Endoperoxide availability which by rat and human endothelial cell prostacycline synthetase can be utilized for increase prostacyclin production.

Neuroprotective Effects of Increased Extracellular Ca2+ During Aglycemia in White Matter

2002 ◽  
Vol 88 (3) ◽  
pp. 1302-1307 ◽  
Author(s):  
Angus M. Brown ◽  
Bruce R. Ransom
Keyword(s):  
Action Potentials ◽  
Divalent Cations ◽  
Neuroprotective Effects ◽  
Adult Rat ◽  
Artificial Cerebrospinal Fluid ◽  
Before And After ◽  
Compound Action Potentials ◽  
Compound Action

We investigated the effects of extracellular [Ca2+] ([Ca2+]o) on aglycemia-induced dysfunction and injury in adult rat optic nerves. Compound action potentials (CAPs) from adult rat optic nerve were recorded in vitro, and the area under the CAP was used to monitor nerve function before and after 1 h periods of aglycemia. In control artificial cerebrospinal fluid (ACSF) containing 2 mM Ca2+, CAP function fell after 29.9 ± 1.5 (SE) min and recovered to 48.8 ± 3.9% following aglycemia. Reducing bath [Ca2+] during aglycemia progressively improved recovery. For example, in Ca2+-free ACSF, the CAP recovered to 99.1 ± 3.8%. Paradoxically, increasing bath [Ca2+] also improved recovery from aglycemia. In 5 or 10 mM bath [Ca2+], CAP recovered to 78.8 ± 9.2 or 91.6 ± 5.2%, respectively. The latency to CAP failure during aglycemia increased as a function of bath [Ca2+] from 0 to 10 mM. Increasing bath [Mg2+] from 2 to 5 or 10 mM, with bath [Ca2+] held at 2 mM, increased latency to CAP failure with aglycemia and improved recovery from this insult. [Ca2+]o recorded with calcium-sensitive microelectrodes in control ACSF, dropped reversibly during aglycemia from 1.54 ± 0.03 to 0.45 ± 0.04 mM. In the presence of higher ambient levels of bath [Ca2+] (i.e., 5 or 10 mM), the aglycemia-induced decrease in [Ca2+]o declined, indicating that less Ca2+ left the extracellular space to enter an intracellular compartment. These results indicate that the role of [Ca2+], and divalent cations in general, during aglycemia is complex. While extracellular Ca2+ was required for irreversible aglycemic injury to occur, higher levels of [Ca2+] or [Mg2+] increased the latency to CAP failure and improved the extent of recovery, apparently by limiting Ca2+ influx. These effects are theorized to be mediated by divalent cation screening.

scholarly journals Sildenafil (Viagra®) Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

2017 ◽  
Vol 44 (5) ◽  
pp. 1796-1809 ◽  
Author(s):  
Marcos A.S. Leal ◽  
Ananda T. Dias ◽  
Marcella L. Porto ◽  
Bruna F. Brun ◽  
Agata L. Gava ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Proinflammatory Cytokines ◽  
Contractile Response ◽  
Wild Type ◽  
Beneficial Effects ◽  
Relative Contribution ◽  
Before And After ◽  
Cox 2 ◽  
Phosphodiesterase 5 ◽  
Cox 1

Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE-/-) mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a) to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2), thromboxane A2 (TXA2) and endothelin-1 (ET-1) to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b) to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks) and compared with non-treated ApoE-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE) in aortic rings were evaluated before and after incubation with Cox-1 (SC-560) or Cox-2 (NS-398) inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE-/- mice exhibited enhanced vasoconstriction to PE (Rmax ∼35%, p<0.01), which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE-/- mice also exhibited enhanced contractions to ET-1 (Rmax ∼30%, p<0.01), which were attenuated in sildenafil-treated ApoE-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1). Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities.

scholarly journals Hydrogen peroxide modulates the contractile response induced by phenylephrine in renal hypertensive rat aorta

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Bruno Rodrigues Silva ◽  
Laena Pernomian ◽  
Marcella Daruge Grando ◽  
Lusiane Maria Bendhack
Keyword(s):  
Hydrogen Peroxide ◽  
Contractile Response ◽  
Rat Aorta ◽  
Hypertensive Rat ◽  
Renal Hypertensive Rat

Endotoxin pretreatment enhances portal venous contractile response to endothelin-1

1996 ◽  
Vol 270 (1) ◽  
pp. H7-H15 ◽  
Author(s):  
B. H. Pannen ◽  
M. Bauer ◽  
J. X. Zhang ◽  
J. L. Robotham ◽  
M. G. Clemens
Keyword(s):  
Contractile Response ◽  
Portal Pressure ◽  
Normal Liver ◽  
Portal Circulation ◽  
Cell Velocity ◽  
Before And After ◽  
Red Blood Cell Velocity ◽  
Regression Slopes ◽  
Escherichia Coli Lipopolysaccharide ◽  
Krebs Buffer

To test whether endotoxin pretreatment modulates the portal hemodynamic response to endothelin (ET)-1 and phenylephrine (PE), two potent vasoconstrictors in the portal circulation of the normal liver, rats received intraperitoneal injections of Escherichia coli lipopolysaccharide (LPS; 1 mg/kg body wt) or saline. Livers were isolated after 6 or 24 h and perfused with Krebs buffer containing 5% autologous erythrocytes. Analyses of portal pressure-flow (P-Q) relationships and epifluorescence video microscopy were performed before and after ET-1 (10(-9) M) or PE (10(-5) M) administration. LPS pretreatment increased total portal resistances (Rt), zero-flow pressures (PQ = 0), and linear regression slopes of P-Q relationships, and decreased the sinusoidal diameters (Ds) and sinusoidal volumetric flow (Qv). The response to ET-1 was enhanced 6 and 24 h after LPS administration, leading to greater increases in Rt, PQ = 0, and slope and more pronounced decreases in Dx, red blood cell velocity (VRBC), and Qv. In contrast, PE effects were similar (PQ = 0, slope, Ds) or even attenuated (Rt, VRBC, Qv) in livers from LPS-treated compared with control animals. Thus endotoxin pretreatment increased the portal contractile response to ET-1 but not to PE. This enhanced ET-1 response appeared to occur at sinusoidal and presinusoidal levels and may contribute to endotoxin-induced hepatic microcirculatory failure.

scholarly journals Metformin exaggerates phenylephrine-induced AMPK phosphorylation independent of CaMKKβ and attenuates contractile response in endothelium-denuded rat aorta

2014 ◽  
Vol 92 (2) ◽  
pp. 266-279 ◽  
Author(s):  
Rajkumar Pyla ◽  
Islam Osman ◽  
Prahalathan Pichavaram ◽  
Paul Hansen ◽  
Lakshman Segar
Keyword(s):  
Contractile Response ◽  
Rat Aorta ◽  
Ampk Phosphorylation
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