scholarly journals Angiopoietin-2 is released during anaphylactic hypotension in anesthetized and unanesthetized rats

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242026
Author(s):  
Tao Zhang ◽  
Toshishige Shibamoto ◽  
Mamoru Tanida ◽  
Makoto Taniguchi ◽  
Yuhichi Kuda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Acute Lung Injury ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Plasma Levels ◽  
Blue Dye ◽  
Arterial Blood ◽  
Tnf Α ◽  
Angiopoietin 2

Angiopoietin (Angpt)-2, a permeability-increasing growth factor, is involved in vascular leakage of sepsis and acute lung injury, and could be released from endothelium in response to anaphylaxis-related secretagogues such as histamine and leukotrienes, or cytokines. However, roles of Angpt-2 in the hyperpermeability during systemic anaphylaxis are not known. Thus, we determined plasma levels of Angpt-2 and cytokines and vascular permeability during anaphylactic hypotension in unanesthetized rats. Anaphylaxis was induced by an intravenous injection of ovalbumin antigen. Mean arterial blood pressure (MBP) was measured, and hematocrit (Hct) and plasma levels of Angpt-2 and cytokines were assessed for 24 h after antigen injection. Separately, vascular permeability was measured in various organs using the Evans blue dye method, and Angpt-2 mRNA expression in liver was measured. After antigen injection, MBP decreased to the nadir at 6 min, and returned to baseline at 45 min, and Hct peaked at 20 min and thereafter progressively declined, suggesting that vascular leak and hypotension occurred within 20 min. Plasma Angpt-2 levels began to increase significantly at 1 h after antigen, reaching the peak 2.7-fold baseline at 6 h with a return to baseline at 24 h. Detected cytokines of IL-1α, IL-1β, IL-6, IL-10, and TNF-α peaked 1 or 2 h after antigen. Angpt-2 mRNA increased at 2 h and showed an increasing tendency at 6 h. Vascular permeability in bronchus, trachea, intestines, mesentery and skeletal muscle was increased at 10 min but not at 6 h after antigen. In addition, we confirmed using anesthetized rat anaphylaxis models that plasma Angpt-2 levels increased at 1 h after antigen. In conclusion, plasma Angpt-2 is elevated presumably due to increased cytokines and enhanced gene transcription during anaphylaxis in anesthetized and unanesthetized rats.

Abstract MP57: Chronic Inhibition Of Brain Rhomboid-like Protein 2 (irhom2) Activity Decreases Arterial Blood Pressure In Salt-sensitive Hypertension In Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Mazher Mohammed ◽  
Mona Elgazzaz ◽  
Clara Berdasco ◽  
Eric D Lazartigues
Keyword(s):  
Blood Pressure ◽  
Neutralizing Antibody ◽  
Experimental Models ◽  
Arterial Blood ◽  
Artificial Cerebrospinal Fluid ◽  
Tnf Α ◽  
Significant Attenuation ◽  
Factor Α ◽  
Salt Sensitive Hypertension ◽  
The Brain

We previously reported that ADAM17 (aka tumor necrosis factor-α convertase) is critical for the development of hypertension in experimental models and patients. Recent studies highlighted that ADAM17’s formation of TNF-α relies on prior maturation of this sheddase, controlled by the rhomboid-like protein 2 (iRhom2) specifically in microglia. Genetic deletion of iRhom2 in mice shows significant attenuation of TNF-α and ADAM17 activity in a tissue specific manner. Here, we hypothesized that silencing iRhom2 activity specifically in the brain would decrease blood pressure (BP) in the DOCA-salt model of hypertension, in mice. Uninephrectomized mice were implanted subcutaneously (sc) with DOCA-pellets (50 mg) and provided with 1% saline in drinking water. In addition, mice were chronically implanted with an icv cannula connected to a sc osmotic minipump for delivery of: (1) iRhom2-siRNA (9.6 μg/kg/day), (2) scrambled siRNA (SCR 0.2 μg/kg/day), (3) ADAM17 antibody (ADAM17-Ab; 23.8 μg/kg/day) or (4) artificial cerebrospinal fluid (aCSF) for 2 weeks while BP was recorded by telemetry. DOCA-salt treatment led to a significant increase in BP in the control groups (SCR: 156 ±3 mmHg and aCSF: 161 ±1 mmHg; n=3/group; p<0.001) compared to baseline values (122 ±2 mmHg; n=12). ICV infusion of iRhom2-siRNA or ADAM17 neutralizing antibody for 2-weeks in DOCA-salt-treated mice resulted in a significant attenuation of BP (iRhom2-siRNA: 152 ±2 mmHg and ADAM17-Ab: 151 ±2 mmHg n=3/group, p<0.001). These data suggest that: 1) Selective silencing of iRhom2 from microglia is as potent as ADAM17 neutralization throughout the brain in lowering BP and 2) iRhom2 is a potential new therapeutic target for the treatment of salt-sensitive hypertension.

Insulin sensitivity and big ET-1 conversion to ET-1 after ETA- or ETB-receptor blockade in humans

2002 ◽  
Vol 93 (6) ◽  
pp. 2112-2121 ◽  
Author(s):  
Gunvor Ahlborg ◽  
Jonas Lindström
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Receptor Blockade ◽  
Receptor Stimulation ◽  
Renal Vasoconstriction ◽  
Arterial Blood ◽  
Etb Receptor

Cardiovascular diseases are characterized by insulin resistance and elevated endothelin (ET)-1 levels. Furthermore, ET-1 induces insulin resistance. To elucidate this mechanism, six healthy subjects were studied during a hyperinsulinemic euglycemic clamp during infusion of (the ET-1 precursor) big ET-1 alone or after ETA- or ETB-receptor blockade. Insulin levels rose after big ET-1 with or without the ETB antagonist BQ-788 ( P < 0.05) but were unchanged after the ETA antagonist BQ-123 + big ET-1. Infused glucose divided by insulin fell after big ET-1 with or without BQ-788 ( P < 0.05). Insulin and infused glucose divided by insulin values were normalized by ETA blockade. Mean arterial blood pressure rose during big ET-1 with or without BQ-788 ( P < 0.001) but was unchanged after BQ-123. Skeletal muscle, splanchnic, and renal blood flow responses to big ET-1 were abolished by BQ-123. ET-1 levels rose after big ET-1 ( P< 0.01) in a similar way after BQ-123 or BQ-788, despite higher elimination capacity after ETA blockade. In conclusion, ET-1-induced reduction in insulin sensitivity and clearance as well as splanchnic and renal vasoconstriction are ETA mediated. ETA-receptor stimulation seems to inhibit the conversion of big ET-1 to ET-1.

Physiological persona differences based on stress and inflammation between meditators and healthy controls

2019 ◽  
Vol 17 (2) ◽  
Author(s):  
Dipti Magan ◽  
Raj Kumar Yadav
Keyword(s):  
Blood Pressure ◽  
Body Mass Index ◽  
Plasma Levels ◽  
Inflammatory Markers ◽  
Tumor Necrosis ◽  
Healthy Controls ◽  
Short Term ◽  
Tnf Α ◽  
Necrosis Factor

AbstractBackgroundNowadays, yoga is endorsed and advised routinely to stay fit and healthy, as well as control many chronic diseases including diabetes type 2, hypertension, coronary artery diseases, etc. Now, our assumption is that those who do regular yoga have different persona than who do not do yoga regularly. We planned to test our hypothesis scientifically, and therefore baseline physiological characteristics with stress and inflammation levels in long-term and short-term meditators and healthy novice controls were analyzed.MethodsIn this retrospective analysis, 97 male participants were included for their Baseline analysis. Fifteen apparently healthy subjects practicing preksha meditation (since >5 years, at least 5 days a week) were included as long-term meditators (LTMs); 58 subjects who attended one of our short-term yoga-based lifestyle intervention programs for 2 weeks were included as short-term meditators (STMs); 24 male novice subjects, who did not participate in any yogic intervention, were included as healthy controls. Here, we analyzed the Baseline plasma levels of stress and inflammatory markers, cortisol, β-endorphin, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in long-term meditators vs. short-term meditators vs. healthy controls.Outcome measuresThe study parameters body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma levels of stress and immune markers, cortisol, β-endorphin (β-Ed), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were assessed in all the three groups at baseline.ResultsSignificant (p<0.05) differences were observed at baseline for plasma levels of stress and inflammatory markers as well as body mass index and systolic blood pressure among LTM vs. STM vs. healthy controls.ConclusionsOur observations suggest that the subjects who do regular yoga-meditation practice have better stress & inflammation status than comparable age matched healthy controls.

Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2240-2245 ◽  
Author(s):  
Alvaro Aguayo ◽  
Hagop Kantarjian ◽  
Taghi Manshouri ◽  
Cristi Gidel ◽  
Elihu Estey ◽  
...  
Keyword(s):  
Growth Factor ◽  
Blood Vessels ◽  
Myelodysplastic Syndromes ◽  
Plasma Levels ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Angiogenic Factors ◽  
Bone Marrow Biopsies ◽  
Tnf Α ◽  
Factor Α

Abstract Angiogenesis has been associated with the growth, dissemination, and metastasis of solid tumors. The aims of this study were to evaluate the vascularity and the levels of angiogenic factors in patients with acute and chronic leukemias and myelodysplastic syndromes (MDS). The numbers of blood vessels were measured in 145 bone marrow biopsies and the levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis growth factor-α (TNF-α), tumor growth factor-α (TGF-α), and hepatocyte growth factor (HGF) were determined in 417 plasma samples. Except for chronic lymphocytic leukemia (CLL), vascularity was significantly higher in all leukemias and MDS compared with control bone marrows. The highest number of blood vessels and largest vascular area were found in chronic myeloid leukemia (CML). VEGF, bFGF, and HGF plasma levels were significantly increased in acute myeloid leukemia (AML), CML, CLL, chronic myelomonocytic leukemia (CMML), and MDS. HGF, TNF-α, and bFGF but not VEGF were significantly increased in acute lymphoblastic leukemia (ALL). TNF-α levels were significantly increased in all diseases except for AML and MDS. No significant increase was found in TGF-α in any leukemia or MDS. The highest plasma levels of VEGF were in CML, and the highest plasma levels of bFGF were in CLL. The levels of HGF were highest in CMML. These data suggest that vascularity and angiogenic factors are increased in leukemias and MDS and may play a role in the leukemogenic process.

Neural control of vascular permeability: interactions between primary afferents, mast cells, and sympathetic efferents

1989 ◽  
Vol 62 (1) ◽  
pp. 48-58 ◽  
Author(s):  
T. J. Coderre ◽  
A. I. Basbaum ◽  
J. D. Levine
Keyword(s):  
Blood Pressure ◽  
Mast Cells ◽  
Vascular Permeability ◽  
Neural Control ◽  
Primary Afferents ◽  
Sympathetic Chain ◽  
Blue Dye ◽  
Base Line ◽  
Plasma Extravasation ◽  
Sympathetic Efferents

1. This study addressed the contribution of primary afferents, mast cells, and sympathetic efferents to the control of vascular permeability in synovial joints. Extravasation of Evans blue dye into the synovial space was measured by perfusion of the knee joint in the adult rat. Plasma extravasation (PE) was evoked by pharmacologic activation of either unmyelinated primary afferents, mast cells, or sympathetic postganglionic nerve (SPGN) terminals with acute injection of either capsaicin, compound 48/80, or 6-hydroxydopamine (6-OHDA), respectively. In otherwise untreated control rats, acute infusion of capsaicin or compound 48/80 produced a brief increase in vascular permeability; infusion of 6-OHDA produced a larger and more prolonged increase. 2. To evaluate the contribution of an interaction of different cellular elements in the joint to PE, we repeated these experiments in rats pretreated with capsaicin, compound 48/80, or 6-OHDA; administered quercetin; or surgically sympathectomized by excision of the lumbar sympathetic chain. Eliminating unmyelinated afferent nerve terminals by neonatal treatment with capsaicin only reduced the increase in PE produced by acute infusion of capsaicin. Degranulating mast cells by pretreatment with compound 48/80, or preventing the degranulation of mast cells by treatment with quercetin, reduced the increase in PE evoked by infusion of either capsaicin or compound 48/80. Finally, sympathectomy, produced by excision of the lumbar sympathetic chain or by pretreatment with 6-OHDA, significantly reduced PE elicited by acute infusion of capsaicin, compound 48/80, or 6-OHDA. 3. Neither infusing substances normally localized to sympathetic efferents nor inducing changes in blood pressure could mimic the profound increase in PE evoked by activation of sympathetic postganglionic neurons with acute infusion of 6-OHDA. Thus norepinephrine produced a significant decrease in PE, adenosine triphosphate produced only a brief increase, neuropeptide Y had no effect, and manipulating blood pressure (either up or down) had no effect on either base-line or 6-OHDA-induced PE. 4. Indomethacin treatment significantly reduced the increase in PE produced by 6-OHDA. This effect of indomethacin was reversed by the addition of prostaglandin E2 (PGE2) to the 6-OHDA in the perfusion fluid. This finding implicates prostaglandins (i.e., cyclooxygenase products of arachidonic acid metabolism) in SPGN-dependent generation of PE.(ABSTRACT TRUNCATED AT 400 WORDS)

Muscle chemoreflex alters vascular conductance in nonischemic exercising skeletal muscle

1994 ◽  
Vol 77 (6) ◽  
pp. 2761-2766 ◽  
Author(s):  
S. W. Mittelstadt ◽  
L. B. Bell ◽  
K. P. O'Hagan ◽  
P. S. Clifford
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Arterial Blood Pressure ◽  
Blood Pressure Response ◽  
Pressor Response ◽  
Vascular Conductance ◽  
Arterial Blood ◽  
Response To Exercise ◽  
Muscle Chemoreflex

Previous studies have shown that the muscle chemoreflex causes an augmented blood pressure response to exercise and partially restores blood flow to ischemic muscle. The purpose of this study was to investigate the effects of the muscle chemoreflex on blood flow to nonischemic exercising skeletal muscle. During each experiment, dogs ran at 10 kph for 8–16 min and the muscle chemoreflex was evoked by reducing hindlimb blood flow at 4-min intervals (0–80%). Arterial blood pressure, hindlimb blood flow, forelimb blood flow, and forelimb vascular conductance were averaged over the last minute at each level of occlusion. Stimulation of the muscle chemoreflex caused increases in arterial blood pressure and forelimb blood flow and decreases in forelimb vascular conductance. The decrease in forelimb vascular conductance demonstrates that the muscle chemoreflex causes vasoconstriction in the nonischemic exercising forelimb. Despite the decrease in vascular conductance, the increased driving pressure caused by the pressor response was large enough to produce an increased forelimb blood flow.

Effect of vasopressors on organ blood flow during endotoxin shock in pigs

1987 ◽  
Vol 252 (2) ◽  
pp. H291-H300 ◽  
Author(s):  
M. J. Breslow ◽  
C. F. Miller ◽  
S. D. Parker ◽  
A. T. Walman ◽  
R. J. Traystman
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Left Ventricle ◽  
Arterial Blood Pressure ◽  
Endotoxin Shock ◽  
Organ Blood Flow ◽  
Shock Model ◽  
Blood Pressure Elevation ◽  
Arterial Blood

A volume-resuscitated porcine endotoxin shock model was used to evaluate the effect on organ blood flow of increasing systemic arterial blood pressure with vasopressors. Administration of 0.05–0.2 mg/kg of Escherichia coli endotoxin (E) reduced mean arterial blood pressure (MAP) to 50 mmHg, decreased systemic vascular resistance to 50% of control, and did not change cardiac output or heart rate. Blood flow to brain, kidney, spleen, and skeletal muscle was reduced during endotoxin shock, but blood flow to left ventricle, small and large intestine, and stomach remained at pre-endotoxin levels throughout the study period. Four groups of animals were used to evaluate the effect of vasopressor therapy. A control group received E and no vasopressor, whereas the other three groups received either norepinephrine, dopamine, or phenylephrine. Vasopressors were administered starting 60 min after E exposure, and the dose of each was titrated to increase MAP to 75 mmHg. Despite the increase in MAP, brain blood flow did not increase in any group. Norepinephrine alone increased blood flow to the left ventricle. Kidney, splanchnic, and skeletal muscle blood flow did not change with vasopressor administration. The dose of norepinephrine required to increase MAP by 20–25 mmHg during E shock was 30 times the dose required for a similar increase in MAP in animals not receiving E. We conclude that hypotension in the fluid resuscitated porcine E shock model is primarily the result of peripheral vasodilatation, that the vascular response to vasoconstrictors in this model is markedly attenuated following E administration, that blood pressure elevation with norepinephrine, dopamine, and phenylephrine neither decreases blood flow to any organ nor increases blood flow to organs with reduced flow, and that norepinephrine, dopamine, and phenylephrine affect regional blood flow similarly in this model.

Mean arterial blood pressure and serum levels of the molar ratio of insulin-like growth factor-1 to its binding protein-3 in healthy centenarians

1999 ◽  
Vol 17 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Giuseppe Paolisso ◽  
Maria Rosaria Tagliamonte ◽  
Maria Rosaria Rizzo ◽  
Mario Rotondi ◽  
Pasquale Gualdiero ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Growth Factor ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Binding Protein ◽  
Serum Levels ◽  
Molar Ratio ◽  
Insulin Like Growth Factor ◽  
Arterial Blood

Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat

2001 ◽  
Vol 90 (3) ◽  
pp. 795-803 ◽  
Author(s):  
John Armour ◽  
Karel Tyml ◽  
Darcy Lidington ◽  
John X. Wilson
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Cecal Ligation ◽  
Microvascular Dysfunction ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Plasma Ascorbate ◽  
Ascorbate Concentration

Septic patients have low plasma ascorbate concentrations and compromised microvascular perfusion. The purpose of the present experiments was to determine whether ascorbate improves capillary function in volume-resuscitated sepsis. Cecal ligation and perforation (CLP) was performed on male Sprague-Dawley rats. The concentration of ascorbate in plasma and urine, mean arterial blood pressure, and density of continuously perfused capillaries in the extensor digitorum longus muscle were measured 24 h after surgery. CLP caused a 50% decrease (from 56 ± 4 to 29 ± 2 μM) in plasma ascorbate concentration, 1,000% increase (from 46 ± 13 to 450 ± 93 μM) in urine ascorbate concentration, 20% decrease (from 115 ± 2 to 91 ± 2 mmHg) in mean arterial pressure, and 30% decrease (from 24 ± 1 to 17 ± 1 capillaries/mm) in the density of perfused capillaries, compared with time-matched controls. A bolus of intravenous ascorbate (7.6 mg/100 g body wt) administered immediately after the CLP procedure increased plasma ascorbate concentration and restored both blood pressure and density of perfused capillaries to control levels. In vitro experiments showed that ascorbate (100 μM) inhibited replication of bacteria and prevented hydrogen peroxide injury to cultured microvascular endothelial cells. These results indicate that ascorbate is lost in the urine during sepsis and that a bolus of ascorbate can prevent microvascular dysfunction in the skeletal muscle of septic animals. Our study supports the view that ascorbate may be beneficial for patients with septic syndrome.

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