scholarly journals Increased receptor expression supports vascular reactivity of the rabbit aorta during preservation

2020 ◽  
Author(s):  
Nelson Ivan Cupitra ◽  
Juan C Calderón ◽  
Raul Narvaez-Sanchez
Keyword(s):  
Potassium Chloride ◽  
Vascular Reactivity ◽  
Thromboxane A2 ◽  
Rabbit Aorta ◽  
Time Frame ◽  
Receptor Expression ◽  
Optimal Time ◽  
Maximum Effect ◽  
Organ Bath ◽  
Significant Deterioration

Abstract OBJECTIVES The mechanistic understanding of vascular functional impairment during preservation time helps determine the optimal time frame in which explanted arteries can be used. The method of choice is to measure vascular reactivity and receptor expression. Our goal was to study the influence of preservation for 24 and 48 h on vascular reactivity and receptor expression in rabbit aorta. METHODS Aortic rings preserved in Krebs–Henseleit solution were evaluated fresh (t0), 24 h (t24) and 48 h (t48) after harvest for (i) vascular reactivity as sensitivity (pD2) and maximum effect in response to potassium chloride, U46619 (thromboxane-A2 agonist), phenylephrine, carbachol and isoproterenol, in an organ bath; and for (ii) expression of α1, β2 and thromboxane-prostanoid receptors, by immunofluorescence. RESULTS Compared to the control, after 24 h of preservation, potassium chloride-induced pD2 increased a significant 3.6%, whereas U46619-induced vasoconstriction decreased 9%. None of the agonists affected vasodilation. Intimal and medial α1 receptor expression increased 2.5-fold. After 48 h of preservation, α1 expression and vasoconstrictor responses remained similar to those after 24 h of preservation, but in vasodilation the carbachol-induced maximum effect decreased 30% whereas isoproterenol-induced pD2 increased 4% and the maximum effect increased 10%. TP and β2 expression in the intima and media increased 1.8- and 2.5-fold, respectively. CONCLUSIONS Up to 48 h of preservation, the adrenergic pathway and its receptors support vasoconstriction and vasodilation, despite a significant deterioration in the prostanoid pathway.

The Effect on Health of Some Cardiovascular Risk Factors

2017 ◽  
Vol 68 (10) ◽  
pp. 2237-2242
Author(s):  
Germaine Savoiu Balint ◽  
Mihaiela Andoni ◽  
Ramona Amina Popovici ◽  
Laura Cristina Rusu ◽  
Ioana Citu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Reactivity ◽  
Vascular Wall ◽  
Dose Effect ◽  
Organ Bath ◽  
Before And After ◽  
Specific Receptors ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Relaxing Response

Arterial endothelium produces a large ramge of active factors which are indispensable for modulation of vasomotor tone and maintenance of vascular wall integrity. From these factors, nitric oxide (NO), wich is released by the endothelial cells as a response to acetylcholine or adenosine action on specific receptors, plays an important role.NO is the result of oxidation process of L-arginine into L-citrulline, under the action of endothelial nitric oxide synthase (NOSe), wich is activated by intracelluar Ca2+ - calmodulin complex . Our study, performed in isolated organ bath, analyzed vascular reactivity of 12 guinea pigs� thoracic aorta rings. After phenylephrine -PHE 10-5 mol/L precontraction, the dose-effect curves for acetylcoline � ACH, adenosine 5� phosphate - 5�ADP and sodium nitroprusside � SNP were determined, before and after incubation of preparation, for 1 hour, with 5% hydrosoluble cigarettes smoke extract (CSE). Statistic analysis, performed with the use of t pair test and ANOVA parametric test, showed that incubation of vascular preparation with 5% CSE has increased the contractile response to PHE 10-5 mol/L (p[0.05), has reduced the endothelium-dependent relaxing response to ATP 10-5 mol/L (p[0.001) and 5�ADP 10-5 molo/L (p[0.001), but has not significantly modified the endothelium-independent relaxing response to SNP 10-5 mol/L (p=0.05). As a conclusion, vascular rings incubation with 5% CSE induced a decrease of endothelium NO synthesis under the action of AXH and 5�ADP, but did not change the smooth muscle fiber respomse in the presence of NO released by SNP.

Construct Validity

2017 ◽  
Author(s):  
Richard McCleary ◽  
David McDowall ◽  
Bradley J. Bartos
Keyword(s):  
Time Series ◽  
Construct Validity ◽  
Hypothesis Test ◽  
Secondary Data ◽  
Time Frame ◽  
Primary Data ◽  
Optimal Time ◽  
Intervention Model ◽  
Right Hand ◽  
The Right

Chapter 8 focuses on threats to construct validity arising from the left-hand side time series and the right-hand side intervention model. Construct validity is limited to questions of whether an observed effect can be generalized to alternative cause and effect measures. The “talking out” self-injurious behavior time series, shown in Chapter 5, are examples of primary data. Researchers often have no choice but to use secondary data that were collected by third parties for purposes unrelated to any hypothesis test. Even in those less-than-ideal instances, however, an optimal time series can be constructed by limiting the time frame and otherwise paying attention to regime changes. Threats to construct validity that arise from the right-hand side intervention model, such as fuzzy or unclear onset and responses, are controlled by paying close attention to the underlying theory. Even a minimal theory should specify the onset and duration of an impact.

scholarly journals Compared Phenolic Compound Contents of 22 Commercial Fruit and Vegetable Juices: Relationship to Ex-Vivo Vascular Reactivity and Potential In Vivo Projection

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 92 ◽  
Author(s):  
Alexis Matute ◽  
Jessica Tabart ◽  
Jean-Paul Cheramy-Bien ◽  
Bernard Pirotte ◽  
Claire Kevers ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Phenolic Compound ◽  
Vascular Reactivity ◽  
Ex Vivo ◽  
Clinical Investigation ◽  
Epigallocatechin Gallate ◽  
Fruit Juices ◽  
Organ Bath ◽  
Total Polyphenol ◽  
Total Anthocyanin

The real impact of polyphenol-rich vegetable and fruit juice intake on cardiovascular health remains a matter of controversy. In the present study, rat aorta segments immersed in an organ bath (OB) were used to explore whether the total polyphenol content and/or individual phenolic compound contents of 22 commercial vegetable (n = 3) and fruit juices [(citrus (n = 5), berries (n = 10), apple (n = 2), pineapple (n = 2)] might be associated with vascular tone. Red juices (particularly blackcurrant) and lemon juice caused the most marked vasorelaxation, its amplitude being endothelium dependent or not according to the volume ratio of juice to initial OB solution Vjuice/VOBS). At volume ratios 5% and 10%, both the juice and OB total polyphenol for all juices and total anthocyanin contents for berry juices significantly correlated with aorta vasorelaxation intensity. This was not the case for total or individual flavonols (except kaempferol) or for total or individual flavanols (except epigallocatechin gallate). If one relates our measured concentrations of individual phenolic compounds in OB to what is known about their physiological concentrations, and given our evidenced correlations between compound concentrations and vasorelaxation intensity, kaempferol, epigallocatechin gallate and peonidin-3-O-glucoside seem to emerge as the interesting phenolic compounds likely to be responsible for the potent vasorelaxation observed with fruit juices, and more particularly blackcurrant ones. Clinical investigation is required, however, to confirm our observations.

Abstract TMP113: Oxidative stress and Extracellular Signal-regulated Kinase (ERK) Play a Key Role in Impairment of Receptor Desensitization and Prolongation of Vascular Reactivity in the Cerebral Artery after Subarachnoid Hemorrhage

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Katsuya Hirano ◽  
Katsuharu Kameda ◽  
Akiko Hanada ◽  
Mayumi Hirano
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Vitamin C ◽  
Transient Response ◽  
Vascular Reactivity ◽  
Contractile Response ◽  
Receptor Expression ◽  
Thrombin Inhibitor ◽  
Receptor Desensitization ◽  
Basilar Arteries

Cerebral vasospasm is a critical determinant in the prognosis of subarachnoid hemorrhage (SAH). The vasospasm is characterized by not only enhanced but also prolonged contraction. The enhanced response is attributable to an increased receptor expression, while a prolonged response is attributable to impaired receptor desensitization. This study addressed this hypothesis and investigated the mechanism underlying a prolonged contraction, using a rabbit SAH model and A7r5 smooth muscle cells. A thrombin receptor (PAR 1 )-activating peptide (PAR 1 AP) induced a transient contraction in the basilar arteries of the control rabbits. The subsequent second stimulation produced 8% of the first response. PAR 1 AP induced an enhanced and prolonged contraction in SAH, and the second stimulation produced a 75% response. Thrombin induced an enhanced and prolonged contraction in SAH. This contraction irreversibly persisted even after terminating thrombin stimulation. The enhancement and prolongation of the contractile response after SAH was further observed with angiotensin II, vasopressin and PGF 2 α. The heparinization of autologous blood or the intrathecal application of a thrombin inhibitor, argatroban, prevented the enhancement of contraction, while they had no effect on the prolongation of the contraction. The addition of vitamin C or tempol to argatroban restored the transient response, tachyphylactic attenuation of the second response and reversibility of thrombin contraction. The amount of malondialdehyde, an indicator of oxidative stress, in the brain tissues increased after SAH, and this increase was prevented by either argatroban or vitamin C. The Ca 2+ responses to thrombin and PAR 1 AP in A7r5 cells exhibited a phenomenon similar to those seen with the contractile response in an SAH model. ERK inhibitors restored the transient response, tachyphylactic attenuation and reversibility of thrombin response, while the inhibitors of JNK, p38 kinase or Rho kinase had no effect. In conclusion, oxidative stress and ERK activation play a key role in the impaired receptor desensitization and prolonged vascular reactivity after SAH. Targeting oxidative stress and ERK could provide a novel strategy to normalize vascular reactivity after SAH.

Aspirin-Dependent Effects on Purinergic P2Y1 Receptor Expression

2019 ◽  
Vol 119 (05) ◽  
pp. 726-734 ◽  
Author(s):  
Isabella Massimi ◽  
Laura Alemanno ◽  
Maria Guarino ◽  
Raffaella Guerriero ◽  
Massimo Mancone ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Thromboxane A2 ◽  
Adenosine Diphosphate ◽  
Receptor Expression ◽  
P2y1 Receptor ◽  
Biochemical Pathway ◽  
Thromboxane A2 Receptor ◽  
Induced Aggregation

AbstractChronic treatment with aspirin in healthy volunteers (HVs) is associated with recovery of adenosine diphosphate (ADP)-induced platelet activation. The purinergic P2Y1 receptor exerts its effects via a Gq-protein, which is the same biochemical pathway activated by thromboxane-A2 receptor. We hypothesized that recovery of ADP-induced platelet activation could be attributed to increased P2Y1 expression induced by chronic aspirin exposure. We performed a multi-phase investigation which embraced both in vitro and in vivo experiments conducted in (1) human megakaryoblastic DAMI cells, (2) human megakaryocytic progenitor cell cultures, (3) platelets obtained from HVs treated with aspirin and (4) platelets obtained from aspirin-treated patients. DAMI cells treated with aspirin or WY14643 (PPARα agonist) had a significant up-regulation of P2Y1 mRNA, which was shown to be a PPARα-dependent process. In human megakaryocytic progenitors, in the presence of aspirin or WY14643, P2Y1 mRNA expression was higher than in mock culture. P2Y1 expression increased in platelets obtained from HVs treated with aspirin for 8 weeks. Platelets obtained from patients who were on aspirin for more than 2 months had increased P2Y1 expression and ADP-induced aggregation compared with patients on aspirin treatment for less than a month. Overall, our results suggest that aspirin induces genomic changes in megakaryocytes leading to P2Y1 up-regulation and that PPARα is the nuclear receptor involved in this regulation. Since P2Y1 is coupled to the same Gq-protein of thromboxane-A2 receptor, platelet adaptation in response to pharmacological inhibition seems not to be receptor specific, but may involve other receptors with the same biochemical pathway.

Lack Of Inhibition Of Thromboxane Production Despite Inhibition Of Platelet Function By 1,3-Bis(2 Chloroethyl)-1-Nitrosourea (BCNU)

1981 ◽  
Author(s):  
R McKenna ◽  
T Ahmad ◽  
A Prancan ◽  
D Simon ◽  
H Frischer
Keyword(s):  
Arachidonic Acid ◽  
Oxygen Consumption ◽  
Platelet Aggregation ◽  
Acetylsalicylic Acid ◽  
Platelet Function ◽  
Human Platelet ◽  
Thromboxane A2 ◽  
Rabbit Aorta ◽  
Thromboxane Production ◽  
Platelet Thromboxane

We have previously shown that BCNU inhibits human platelet glutathione reductase (GSSG-R) prior to inhibiting platelet function; since thromboxane production is important in platelet function, we evaluated the effect of BCNU induced inhibition of GSSG-R on platelet thromboxane production.Control platelet GSSG-R activity was 0.091 ]jmoles NAD(P)H oxidized min-1lmg-1 protein at 37°C (±0.015 S.D.; n=9); inhibition was detectable at 10-7M% BCNU (70% of control) with a >90% inhibition at and above 10-5M BCNU. Platelet aggregation in response to 1.5×10-3M Arachidonic acid (AA), 10 μM epinephrine, 6 μg/ml equine collagen and 3 μM ADP were inhibited at 10-5M BCNU and abolished at 10-4 BCNU.BCNU (10-3M) did not affect the increase in oxygen consumption induced by AA. Using the rabbit aorta superfusion bioassay for thromboxane A2 (TXA2), threshold concentrations of AA in 10-5 and 10-4 BCNU platelets resulted in an increased measure of aortic tension 13.5 ± 9.4 mm S.D. (n=6) and 23.2 ± 9.5 mm respectively, compared with control values of 4.5 ± 2.4. Acetylsalicylic acid (5 × l0-4M) inhibited the contraction: 1.7 ± 1.1 (n=5). The conversion of 14C AA to thromboxane B2 (TXB2) and PGE2, as measured by radio TLC, was not decreased in BCNU treated platelets. There is a significant increase in TXB2 (p<0.05;n=4) and in the ratio of TXB2:PGE2 in platelets treated with 10-4M BCNU and 10-3M imidazole when compared to platelets treated with imidazole alone.In conclusion BCNU induced inhibition of platelet GSSG-R and platelet function occurs despite preservation of thromboxane production

scholarly journals Physiological and Biochemical Vascular Reactivity Parameters of Angiotensin II and the Action of Biased Agonist TRV023

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Marcos André Soares Leal ◽  
Thanisia de Almeida ◽  
João Guilherme Torres ◽  
Luciene Cristina Gastalho Campos ◽  
Elisardo Corral Vasquez ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Renin Angiotensin System ◽  
Aortic Ring ◽  
Experimental Models ◽  
Organ Bath ◽  
Angiotensin System ◽  
Active Peptides ◽  
Pharmacological Studies ◽  
Physiological And Biochemical

Vascular reactivity experiments using isolated aortic rings have been widely used as a model for physiological and pharmacological studies since the early sixties. Here, we suggest several parameters that the researcher should pay attention to when investigating angiotensin II in their experimental models. Angiotensin II is one of the active peptides of the renin-angiotensin system and exerts its effect through the AT1 and AT2 receptors. Some studies seek to understand the effects of angiotensin II receptors at the vascular level by using vascular reactivity experiments. However, because of the large number of variations, there are only a handful of reactivity studies that seek to use this method. Thus, the objective of this study was to standardize experimental methods with angiotensin II, through vascular reactivity protocols. For this, variables such as basal tension, concentration interval, single concentration, curve concentration response, and multiple experiments using the same aortic ring were developed using the technique of vascular reactivity in an organ bath. This is the first study that has standardized the vascular reactivity protocol. In addition, we demonstrated the effects of TRV023-biased ligand of the AT1R at vascular sites.

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