scholarly journals Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway

2020 ◽  
Vol 21 (18) ◽  
pp. 6569
Author(s):  
Philippe Bonnin ◽  
Christiane Charriaut-Marlangue ◽  
Julien Pansiot ◽  
Alexandre Boutigny ◽  
Jean-Marie Launay ◽  
...  
Keyword(s):  
Blood Flow ◽  
Matched Control ◽  
Parp Inhibitor ◽  
Percentage Increase ◽  
Blood Flows ◽  
Pathway Activation ◽  
Polymerase Inhibitor ◽  
Flow Through ◽  
Blood Flow Velocities

The poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 has been reported to improve endothelial dysfunction in the peripheral system. We addressed the role of PJ34 on the vascular tone and vasoreactivity during development in the mouse brain. Blood flows were measured in the basilar trunk using ultrasonography. Cerebral vasoreactivity or vasodilation reserve was estimated as a percentage increase in mean blood flow velocities (mBFV) recorded under normoxia-hypercapnia in control and after PJ34 administration. Non-selective and selective eNOS and nNOS inhibitors were used to evaluate the role of NO-pathway into the hemodynamic effects of PJ34. PJ34 increased mBFVs from 15.8 ± 1.6 to 19.1 ± 1.9 cm/s (p = 0.0043) in neonatal, from 14.6 ± 1.4 to 16.1 ± 0.9 cm/s (p = 0.0049) in adult, and from 15.7 ± 1.7 to 17.5 ± 2.0 cm/s (p = 0.0024) in aged mice 48 h after administration. These PJ34 values were similar to those measured in age-matched control mice under normoxia-hypercapnia. This recruitment was mediated through the activation of constitutive NO synthases in both the neonatal (38.2 ± 6.7 nmol/min/mg protein) and adult (31.5 ± 4.4 nmol/min/mg protein) brain, as compared to age-matched control brain (6.9 ± 0.4 and 6.3 ± 0.7 nmol/min/mg protein), respectively. In addition, quite selective eNOS inhibitor was able to inhibit the recruitment. PJ34 by itself is able to increase cerebral blood flow through the NO-pathway activation at least over 48 h after a single administration.

Role of renal medullary adenosine in the control of blood flow and sodium excretion

1999 ◽  
Vol 276 (3) ◽  
pp. R790-R798 ◽  
Author(s):  
Ai-Ping Zou ◽  
Kasem Nithipatikom ◽  
Pin-Lan Li ◽  
Allen W. Cowley
Keyword(s):  
Blood Flow ◽  
Sodium Excretion ◽  
Renal Medulla ◽  
Urine Flow ◽  
Doppler Flowmetry ◽  
Blood Flows ◽  
Medullary Blood Flow ◽  
Adenosine Concentration ◽  
Interstitial Infusion

This study determined the levels of adenosine in the renal medullary interstitium using microdialysis and fluorescence HPLC techniques and examined the role of endogenous adenosine in the control of medullary blood flow and sodium excretion by infusing the specific adenosine receptor antagonists or agonists into the renal medulla of anesthetized Sprague-Dawley rats. Renal cortical and medullary blood flows were measured using laser-Doppler flowmetry. Analysis of microdialyzed samples showed that the adenosine concentration in the renal medullary interstitial dialysate averaged 212 ± 5.2 nM, which was significantly higher than 55.6 ± 5.3 nM in the renal cortex ( n = 9). Renal medullary interstitial infusion of a selective A1antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 300 pmol ⋅ kg−1 ⋅ min−1, n = 8), did not alter renal blood flows, but increased urine flow by 37% and sodium excretion by 42%. In contrast, renal medullary infusion of the selective A2 receptor blocker 3,7-dimethyl-1-propargylxanthine (DMPX; 150 pmol ⋅ kg−1 ⋅ min−1, n = 9) decreased outer medullary blood flow (OMBF) by 28%, inner medullary blood flows (IMBF) by 21%, and sodium excretion by 35%. Renal medullary interstitial infusion of adenosine produced a dose-dependent increase in OMBF, IMBF, urine flow, and sodium excretion at doses from 3 to 300 pmol ⋅ kg−1 ⋅ min−1( n = 7). These effects of adenosine were markedly attenuated by the pretreatment of DMPX, but unaltered by DPCPX. Infusion of a selective A3receptor agonist, N 6-benzyl-5′-( N-ethylcarbonxamido)adenosine (300 pmol ⋅ kg−1 ⋅ min−1, n = 6) into the renal medulla had no effect on medullary blood flows or renal function. Glomerular filtration rate and arterial pressure were not changed by medullary infusion of any drugs. Our results indicate that endogenous medullary adenosine at physiological concentrations serves to dilate medullary vessels via A2 receptors, resulting in a natriuretic response that overrides the tubular A1 receptor-mediated antinatriuretic effects.

BLOOD FLOW THROUGH A CIRCULAR PIPE WITH AN IMPULSIVE PRESSURE GRADIENT

2000 ◽  
Vol 10 (02) ◽  
pp. 187-202 ◽  
Author(s):  
GIUSEPPE PONTRELLI
Keyword(s):  
Blood Flow ◽  
Finite Difference ◽  
Finite Difference Method ◽  
Unsteady Flow ◽  
Pressure Gradient ◽  
Collocation Method ◽  
Difference Method ◽  
Flow Through ◽  
Impulsive Pressure

The unsteady flow of a viscoelastic fluid in a straight, long, rigid pipe, driven by a suddenly imposed pressure gradient is studied. The used model is the Oldroyd-B fluid modified with the use of a nonconstant viscosity, which includes the effect of the shear-thinning of many fluids. The main application considered is in blood flow. Two coupled nonlinear equations are solved by a spectral collocation method in space and the implicit trapezoidal finite difference method in time. The presented results show the role of the non-Newtonian terms in unsteady phenomena.

scholarly journals Evolutionary Role of Epigenetics in Ischemic Stroke: A Review

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1616-1620
Author(s):  
Rohini Agrawal ◽  
Prashant Amale ◽  
Shilpa Deshpande ◽  
Manish Deshmukh ◽  
Priti Bhoyar ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Hemorrhagic Stroke ◽  
Neural Stem Progenitor Cells ◽  
Genetic Level ◽  
Flow Through ◽  
After Cancer ◽  
The Brain ◽  
Global Population

Stroke is a Central Nervous System (CNS) disorder which occurs due to the obstruction in the brain blood flow. Stroke is mainly of two types, such as ischemic and hemorrhagic stroke. Ischemic stroke (80%) caused due to obstruction of blood flow through Middle Cerebral Artery (MCA) and characterized by a decreased supply of oxygen and glucose to CNS. In comparison, Hemorrhagic stroke (20%) mainly occurs due to the rupturing of blood vessels. Epidemiologically, it is the common reason of death after cancer and affecting millions of global population. There are many risk factors such as hypertension; hypercholesterolemia etc. which can exaggerate the condition of stroke. Various conventional therapies like Antiplatelets, Thrombolytic are available, but, there is a need to obtain a therapeutic approach that can provide prevention as well as a cure for the stroke. So the present review is primarily focused on epigenetic approach for ischemic stroke by Endogenous Transplantation of Neural Stem/Progenitor Cells (NSPCs). This, in turn, will decrease the level of REST protein at the genetic level and enhance the activity of Na+-Ca+ exchanger activity and lowers the excitotoxicity.

Role of chemical factors in regulation of flow through kidney, hindlimb, and heart

1965 ◽  
Vol 208 (5) ◽  
pp. 813-824 ◽  
Author(s):  
J. B. Scott ◽  
R. M. Daugherty ◽  
J. M. Dabney ◽  
F. J. Haddy
Keyword(s):  
Blood Flow ◽  
Metabolic Rate ◽  
Flow Resistance ◽  
Reactive Hyperemia ◽  
Venous Outflow ◽  
Chemical Factors ◽  
Study Support ◽  
Dog Blood ◽  
Flow Through

In the anesthetized dog, blood flow or metabolic rate was varied in kidney, hindlimb, or heart (experimental organ) while simultaneously diverting a portion of the venous outflow through forelimb or kidney (bioassay organ). The resistance to blood flow through the experimental organ gradually rose in the first few minutes following a large increase in flow and gradually fell following a large decrease in flow. Resistance to blood flow through an experimental organ (hindlimb) fell following increase in metabolic rate. In each case, bioassay organ resistance changed in the same direction when the assay organ was the forelimb and in the opposite direction when the assay organ was the kidney. These findings suggest that active hyperemia, reactive hyperemia, and autoregulation of blood flow result, at least in part, from alteration in the chemical environment of the blood vessels. Other findings in this study support the possibility that adenosine triphosphate contributes to the change in environment.

Role of glucagon in intestinal hyperemia associated with early experimental diabetes mellitus

1988 ◽  
Vol 255 (5) ◽  
pp. G542-G546
Author(s):  
L. F. Yrle ◽  
J. K. Smith ◽  
J. N. Benoit ◽  
D. N. Granger ◽  
R. J. Korthuis
Keyword(s):  
Diabetes Mellitus ◽  
Blood Flow ◽  
Gastrointestinal Tract ◽  
Experimental Diabetes ◽  
Reference Sample ◽  
Diabetic Rats ◽  
Experimental Diabetes Mellitus ◽  
Blood Flows ◽  
Sample Technique

The role of glucagon as a blood-borne mediator of the intestinal hyperemia associated with experimental diabetes mellitus was assessed in anesthetized fasted (18-24 h) rats 4 wk after the administration of streptozotocin (65 mg/kg body wt) or its vehicle. Selective removal of pancreatic glucagon from the circulation was accomplished by the intravenous administration of a highly specific glucagon antiserum. Blood flow to the gastrointestinal tract and kidneys was measured with radioactive microspheres using the reference sample technique. Blood flows were increased by at least 60% in each segment of the gastrointestinal tract of diabetic animals compared with control rats. Glucagon antiserum had no effect on blood flows in the gastrointestinal tract of control animals. However, the antiserum produced a significant reduction in blood flow to the stomach (26%), duodenum (25%), jejunum (12%), and kidneys (16%) in diabetic rats. There was no change in blood flow to the ileum or colon of diabetic animals with antiserum administration. The results of this study support the hypothesis that glucagon mediates a portion of the hyperemia noted in the stomach, duodenum, and jejunum. However, glucagon does not appear to play a role in the genesis of the hyperemia noted in more distal segments of the gastrointestinal tract (ileum and colon). A possible role for glucagon in the maintenance of renal blood flow in diabetic rats is suggested.

A study of the deformability of red blood cells of a teleost fish, the yellowtail (Seriola quinqueradiata), and a comparison with human erythrocytes

1982 ◽  
Vol 96 (1) ◽  
pp. 209-220
Author(s):  
G. M. Hughes ◽  
Y. Kikuchi ◽  
H. Watari
Keyword(s):  
Blood Flow ◽  
Red Blood Cells ◽  
Human Blood ◽  
Blood Cells ◽  
Blood Flow Rate ◽  
Blood Flows ◽  
Human Red Blood Cells ◽  
Seriola Quinqueradiata ◽  
Flow Through ◽  
Environmental Temperatures

The blood of a carangid fish, the yellowtail (Seriola quinqueradiata) has been studied with particular reference to the deformability properties of the red blood cells. The rate at which blood flows through a Nuclepore filter containing 5 micrometers pores has been determined under the same conditions that have been used with human blood. Marked differences were found in the flow of yellowtail blood which depended on the particular way in which the blood had been sampled. Such differences seem to be due to a sensitivity of fish red blood cells to their environmental conditions. Blood flow through filters is temperature-dependent, the rate increasing with a rise in temperature. Measurements made at 37 degrees C gave values which were similar to those normally obtained for human red blood cells, in spite of their greater dimensions (10.4 × 6.8 × 3.4 micrometers), and nucleated nature. It was also found that the blood flow rate of human blood was slower than that of yellowtail blood when measured at the normal environmental temperatures (15 degrees C) for these fish.

scholarly journals Vasodilator tone in the llama fetus: the role of nitric oxide during normoxemia and hypoxemia

2005 ◽  
Vol 289 (3) ◽  
pp. R776-R783 ◽  
Author(s):  
Emilia M. Sanhueza ◽  
Raquel A. Riquelme ◽  
Emilio A. Herrera ◽  
Dino A. Giussani ◽  
Carlos E. Blanco ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Vascular Resistance ◽  
Control Group ◽  
Blood Flows ◽  
Vasoconstrictor Effect ◽  
Vascular Beds ◽  
Oxide Synthase

The fetal llama responds to hypoxemia, with a marked peripheral vasoconstriction but, unlike the sheep, with little or no increase in cerebral blood flow. We tested the hypothesis that the role of nitric oxide (NO) may be increased during hypoxemia in this species, to counterbalance a strong vasoconstrictor effect. Ten fetal llamas were operated under general anesthesia. Mean arterial pressure (MAP), heart rate, cardiac output, total vascular resistance, blood flows, and vascular resistances in cerebral, carotid and femoral vascular beds were determined. Two groups were studied, one with nitric oxide synthase (NOS) blocker NG-nitro-l-arginine methyl ester (l-NAME), and the other with 0.9% NaCl (control group), during normoxemia, hypoxemia, and recovery. During normoxemia, l-NAME produced an increase in fetal MAP and a rapid bradycardia. Cerebral, carotid, and femoral vascular resistance increased and blood flow decreased to carotid and femoral beds, while cerebral blood flow did not change significantly. However, during hypoxemia cerebral and carotid vascular resistance fell by 44% from its value in normoxemia after l-NAME, although femoral vascular resistance progressively increased and remained high during recovery. We conclude that in the llama fetus: 1) NO has an important role in maintaining a vasodilator tone during both normoxemia and hypoxemia in cerebral and femoral vascular beds and 2) during hypoxemia, NOS blockade unmasked the action of other vasodilator agents that contribute, with nitric oxide, to preserving blood flow and oxygen delivery to the tissues.

scholarly journals Poly(ADP-Ribose) Polymerase Inhibitor PJ34 Reduces Brain Damage after Stroke in the Neonatal Mouse Brain

2021 ◽  
Vol 43 (1) ◽  
pp. 301-312
Author(s):  
Philippe Bonnin ◽  
Tania Vitalis ◽  
Leslie Schwendimann ◽  
Alexandre Boutigny ◽  
Nassim Mohamedi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Mouse Brain ◽  
Somatostatin Receptor ◽  
Neurovascular Unit ◽  
Neonatal Mouse ◽  
Tissue Loss ◽  
Polymerase Inhibitor ◽  
Blood Flow Velocities ◽  
Neonatal Ischemia ◽  
The Right

The poly(ADP-ribose) polymerase inhibitor PJ34 has recently been reported to increase cerebral blood flow, via the endothelial NO synthase, in the naive mouse brain throughout life. We addressed here the benefits of PJ34 after neonatal ischemia on hemodynamics and components of the neurovascular unit including the blood-brain barrier (BBB), microglia, and astrocytes. Nine-day-old mice were subjected to permanent MCA occlusion (pMCAo), and treated with either PBS or PJ34 (10 mg/kg). Mean blood-flow velocities (mBFV) were measured in both internal carotid arteries (ICA) and basilar trunk (BT) using Doppler-ultrasonography. BBB opening was assessed through somatostatin-receptor type-2 internalization and immunohistochemistry at 24 and 48 h. Lesion areas were measured 8 days after ischemia. In PBS-treated mice, pMCAo involved a drop in mBFV in the left ICA (p < 0.001 vs. basal), whereas mBFV remained stable in both right ICA and BT. PJ34 prevented this drop in the left ICA (NS vs. basal) and increased mBFV in the right ICA (p = 0.0038 vs. basal). No modification was observed in the BT. In contrast to PBS, BBB disruption extent and astrocyte demise were reduced in PJ34 mice only in the rostral brain at 48 h and 8 days post-pMCAo, respectively. Accordingly, 8 days after pMCAo, affected areas were reduced in the rostral brain (Bregma +0.86 and +0.14 mm), whereas total tissue loss was not reduced after PJ34 (4.0 ± 3.1%) vs. PBS (5.8 ± 3.4%). These results show that PJ34 reduced BBB permeability, astrocyte demise, and tissue loss (particularly in the rostral territories), suggesting that collateral supply mainly proceeds from the anterior ICA’s branches in the ischemic neonatal mouse brain.

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