Effects of indomethacin on PMA-induced pulmonary endothelial enzyme dysfunction in vivo

1992 ◽  
Vol 262 (2) ◽  
pp. L153-L162 ◽  
Author(s):  
X. Chen ◽  
S. E. Orfanos ◽  
J. D. Catravas
Keyword(s):  
Blood Flow ◽  
Left Lung ◽  
Substrate Utilization ◽  
Endothelial Damage ◽  
Metabolic Dysfunction ◽  
Before And After ◽  
Entire Lung ◽  
Metabolically Healthy ◽  
Microvascular Recruitment

We investigated the effects of phorbol myristate acetate (PMA) on metabolic pulmonary endothelial ectoenzyme dysfunction. Anesthetized rabbits were placed on total heart bypass, and the single-pass transpulmonary metabolism of [3H]benzoyl-Phe-Ala-Pro (BPAP) by endothelial-bound angiotensin-converting enzyme (ACE) and [14C]adenosine 5'-monophosphate (AMP) by 5'-nucleotidase (NCT) was calculated before and after PMA (10 micrograms/kg iv), a dose that does not produce histologically evident endothelial damage. Under conditions of partial microvascular recruitment (blood flow = 400 ml/min through the entire lung), PMA, but not the vehicle, significantly reduced substrate utilization of both BPAP and adenosine 5'-monophosphate (AMP) and increased the apparent Michaelis constant (Km) values of ACE for BPAP, indicative of metabolic dysfunction. These changes were completely prevented by pretreatment with indomethacin. Under conditions of near full microvascular recruitment (blood flow = 640 ml/min through the left lung only), PMA similarly reduced substrate utilization and increased the apparent Km of ACE for BPAP. In this case, however, indomethacin failed to prevent the observed PMA-induced metabolic dysfunction. We conclude that PMA alters endothelial ectoenzyme substrate metabolism independently from changes in pulmonary blood flow; indomethacin appears to antagonize the effects of PMA under conditions of partial microvascular recruitment only, perhaps by diverting flow to previously unperfused, unexposed to PMA, and hence metabolically healthy vessels.

Effects of blood flow on lung ACE kinetics: evidence for microvascular recruitment

1991 ◽  
Vol 71 (6) ◽  
pp. 2244-2254 ◽  
Author(s):  
H. J. Toivonen ◽  
J. D. Catravas
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Pulmonary Arterial Pressure ◽  
Left Lung ◽  
In Vivo Assays ◽  
Vascular Bed ◽  
Pulmonary Arterial ◽  
Microvascular Recruitment ◽  
The Relationship

The parameter Amax/Km (product of reactant enzyme mass in perfused microvessels and the constant kcat/Km), calculated from in vivo assays of pulmonary endothelial ectoenzymes (e.g., angiotensin-converting enzyme, ACE), can provide estimates of the perfused pulmonary microvascular surface area (PMSA) in the absence of enzyme dysfunction. We examined the relationship between PMSA and pulmonary blood flow (Qb) in anesthetized rabbits placed on total heart bypass, using [3H]benzoyl-Phe-Ala-Pro (BPAP) as the ACE substrate. When Qb was increased from 250 to 1,100 ml/min, at zone 3 conditions, pulmonary arterial pressure increased, pulmonary vascular resistance (PVR) decreased, and Amax/Km increased linearly, reflecting increasing PMSA. When only the left lung was perfused, increasing Qb from 250 to 636 +/- 17 ml/min (the last value representing fully recruited and/or distended vascular bed), PVR decreased, while Amax/Km increased. When Qb was further increased to 791 +/- 44 ml/min, both PVR and Amax/Km remained unchanged, confirming the lack of additional changes in PMSA. We conclude that Amax/Km provides a sensitive indication of PMSA, because it 1) increases with increasing Qb and decreasing PVR, 2) reaches a maximum at Qb values that correspond to the minimal values in PVR, and 3) like PVR, did not change with further increases in Qb. Compared with predicted changes in PMSA produced by either microvascular recruitment alone or distension alone, our data indicate that recruitment is a larger contributor to the observed increase in PMSA.

scholarly journals Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 964
Author(s):  
Jana Möckel ◽  
Julia Brangsch ◽  
Carolin Reimann ◽  
Jan O. Kaufmann ◽  
Ingolf Sack ◽  
...  
Keyword(s):  
Inductively Coupled Plasma ◽  
Endothelial Damage ◽  
Plaque Burden ◽  
Signal Loss ◽  
Inductively Coupled ◽  
Before And After ◽  
Plasma Mass Spectrometry ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Study

Atherosclerosis is a progressive inflammatory vascular disease characterized by endothelial dysfunction and plaque burden. Extracellular matrix (ECM)-associated plasma proteins play an important role in disease development. Our magnetic resonance imaging (MRI) study investigates the feasibility of using two different molecular MRI probes for the simultaneous assessment of ECM-associated intraplaque albumin deposits caused by endothelial damage and progressive inflammation in atherosclerosis. Male apolipoprotein E-deficient (ApoE-/-)-mice were fed a high-fat diet (HFD) for 2 or 4 months. Another ApoE-/--group was treated with pravastatin and received a HFD for 4 months. T1- and T2*-weighted MRI was performed before and after albumin-specific MRI probe (gadofosveset) administration and a macrophage-specific contrast agent (ferumoxytol). Thereafter, laser ablation inductively coupled plasma mass spectrometry and histology were performed. With advancing atherosclerosis, albumin-based MRI signal enhancement and ferumoxytol-induced signal loss areas in T2*-weighted MRI increased. Significant correlations between contrast-to-noise-ratio (CNR) post-gadofosveset and albumin stain (R2 = 0.78, p < 0.05), and signal loss areas in T2*-weighted MRI with Perls’ Prussian blue stain (R2 = 0.83, p < 0.05) were observed. No interference of ferumoxytol with gadofosveset enhancement was detectable. Pravastatin led to decreased inflammation and intraplaque albumin. Multi-target MRI combining ferumoxytol and gadofosveset is a promising method to improve diagnosis and treatment monitoring in atherosclerosis.

Hemodynamic effects of leukotriene C4 in ovine fetus

1990 ◽  
Vol 259 (6) ◽  
pp. E851-E855
Author(s):  
B. A. Meyer ◽  
S. W. Walsh ◽  
V. M. Parisi
Keyword(s):  
Blood Flow ◽  
Vena Cava ◽  
Cardiovascular Effects ◽  
In Vivo Studies ◽  
Leukotriene C4 ◽  
Blood Flows ◽  
Before And After ◽  
Placental Blood ◽  
Near Term

Leukotrienes are synthesized during pregnancy and produce cardiovascular effects in adults. We hypothesized that leukotriene C4 would cause vasoconstriction in the fetus and placenta. Eight near-term, unanesthetized ovine fetuses were studied before and after infusion of 10 micrograms leukotriene C4 (LTC4) into the fetal vena cava. Cardiovascular monitoring of maternal and fetal arterial pressures and heart rates was performed. Fetal blood flows were measured by the radioactive-microsphere technique. Sustained elevations in systolic and diastolic blood pressure and decreased fetal heart rate began by 1 min and returned to baseline by 30 min. Arterial pH fell from 7.33 +/- 0.01 to 7.29 +/- 0.01 at 15 min (P less than 0.05) and to 7.29 +/- 0.01 at 30 min (P less than 0.05), with a significant increase in base deficit from 0.7 +/- 0.7 to 3.5 +/- 0.7 at 15 min (P less than 0.05) and to 2.9 +/- 1.0 at 30 min (P less than 0.05). Fetal PO2 and PCO2 were unchanged. Significant decreases in blood flow and resistance were seen in the umbilical placental circulation as well as in fetal skeletal muscle and intestine. Blood flow and resistance were unchanged in the renal and adrenal vascular beds. Fetal administration of LTC4 caused no changes in maternal cardiovascular parameters. These findings represent the first in vivo studies of the effects of a lipoxygenase metabolite on fetal-placental blood flow.

Ultrasonographic Bioinformatics Analysis of Uterus After Myomectomy

2020 ◽  
Vol 10 (6) ◽  
pp. 1374-1378
Author(s):  
Lili Jiang ◽  
Chuanxin Cheng ◽  
Xinmei Sheng
Keyword(s):  
Blood Flow ◽  
Bioinformatics Analysis ◽  
Uterine Wall ◽  
Before And After ◽  
The Mean

Objective: The myomectomy will affect the shape of uterine wall. Ultrasound can analyze the bioinformatics characteristics of uterus such as shape and blood flow in vivo. The aim of this study is to analyze the ultrasonographic bioinformatics of uterus after myomectomy. Methods: A total of 127 patients underwent myomectomy were examined by ultrasonography before operation, and 7 d, 1 m, 3 m, and 6 m after operation. The changes of uterine echo and blood signals were observed and recorded. Results: The mean volume of uterus was (152 ± 64) cm3 before myomectomy. During 6 m after operation, the uterus volume in all patients was decreased gradually. At 7 d and 1 m after operation, the mean volume of uterus was (73 ± 22) cm3 and (54 ± 23) cm3, respectively (about 48% and 36% of volume before operation). Different degree of scar echo appeared in 43 patients (33.8%). The diameter of scars was decreased remarkably during 6 months after myomectomy, especially 1 month after operation. Conclusion: The bioinformatics characteristics of uterus changed obviously before and after myomectomy. Ultrasonography is useful to evaluate these changed.

Spiral Laminar Flow in Vivo

1996 ◽  
Vol 91 (1) ◽  
pp. 17-21 ◽  
Author(s):  
P. A. Stonebridge ◽  
P. R. Hoskins ◽  
P.L. Allan ◽  
J. F. F. Belch
Keyword(s):  
Blood Flow ◽  
Reverse Flow ◽  
Arterial Disease ◽  
Flow Patterns ◽  
Endothelial Damage ◽  
Arterial Blood Flow ◽  
Arterial Tree ◽  
Arterial Blood ◽  
Blood Flow Patterns

1. Blood flow patterns are poorly understood despite their impact on arterial disease. There have been few measurements in vivo of the three-dimensional blood flow patterns; we present the results of such studies using a new non-invasive in-vivo method of examining biplanar arterial blood flow patterns. 2. Multiple colour Doppler ultrasound directional velocity images were obtained at two different beam target angles from the artery in the plane perpendicular to its axis. Ensemble average images were constructed; the absolute velocity and direction were calculated by compounding the left and right averaged images. Simple directional, non-directional velocity and vector maps were constructed. 3. Flow patterns were sampled in 11 healthy male volunteers at four points of the pulse cycle; peak systole, systolic downswing, diastolic reverse flow and diastolic forward flow and at three sites; the right common and distal superficial femoral and the left common femoral arteries. 4. Stable rotational flow was observed in all subjects, the direction of rotation varying between sides and individuals. 5. There are theoretical advantages to spiral laminar blood flow; the forward-directed, rotationally induced stability and reduction of laterally directed forces may reduce turbulence in the tapering branching arterial tree and at stenoses and have a beneficial effect on mechanisms of endothelial damage and repair.

Sodium channels are required during in vivo sodium chloride hyperosmolarity to stimulate increase in intestinal endothelial nitric oxide production

2005 ◽  
Vol 288 (1) ◽  
pp. H89-H95 ◽  
Author(s):  
Brett G. Zani ◽  
H. Glenn Bohlen
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Intestinal Blood Flow ◽  
No Production ◽  
Sodium Ions ◽  
Major Mechanism ◽  
Before And After ◽  
Endothelial Nitric Oxide

NaCl hyperosmolarity increases intestinal blood flow during food absorption due in large part to increased NO production. We hypothesized that in vivo, sodium ions enter endothelial cells during NaCl hyperosmolarity as the first step to stimulate an increase in intestinal endothelial NO production. Perivascular NO concentration ([NO]) and blood flow were determined in the in vivo rat intestinal microvasculature at rest and under hyperosmotic conditions, 330 and 380 mosM, respectively, before and after application of bumetanide (Na+-K+-2Cl− cotransporter inhibitor) or amiloride (Na+/H+ exchange channel inhibitor). Suppressing amiloride-sensitive Na+/H+ exchange channels diminished hypertonicity-linked increases in vascular [NO], whereas blockade of Na+-K+-2Cl− channels greatly suppressed increases in vascular [NO] and intestinal blood flow. In additional experiments we examined the effect of sodium ion entry into endothelial cells. We proposed that the Na+/Ca2+ exchanger extrudes Na+ in exchange for Ca2+, thereby leading to the calcium-dependent activation of endothelial nitric oxide synthase (eNOS). We blocked the activity of the Na+/Ca2+ exchanger during 360 mosM NaCl hyperosmolarity with KB-R7943; complete blockade of increased vascular [NO] and intestinal blood flow to hyperosmolarity occurred. These results indicate that during NaCl hyperosmolarity, sodium ions enter endothelial cells predominantly through Na+-K+-2Cl− channels. The Na+/Ca2+ exchanger then extrudes Na+ and increases endothelial Ca2+. The increase in endothelial Ca2+ causes an increase in eNOS activity, and the resultant increase in NO increases intestinal arteriolar diameter and blood flow during NaCl hyperosmolarity. This appears to be the major mechanism by which intestinal nutrient absorption is coupled to increased blood flow.

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin

2003 ◽  
Vol 285 (1) ◽  
pp. E123-E129 ◽  
Author(s):  
M. A. Vincent ◽  
E. J. Barrett ◽  
J. R. Lindner ◽  
M. G. Clark ◽  
S. Rattigan
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Glucose Disposal ◽  
Total Blood ◽  
Artery Flow ◽  
Microvascular Recruitment ◽  
Total Blood Flow

We examined the effects of inhibiting nitric oxide synthase with Nω-nitro-l-arginine-methyl ester (l-NAME) on total hindlimb blood flow, muscle microvascular recruitment, and hindlimb glucose uptake during euglycemic hyperinsulinemia in vivo in the rat. We used two independent methods to measure microvascular perfusion. In one group of animals, microvascular recruitment was measured using the metabolism of exogenously infused 1-methylxanthine (1-MX), and in a second group contrast-enhanced ultrasound (CEU) was used. Limb glucose uptake was measured by arterial-venous concentration differences after 2 h of insulin infusion. Saline alone did not alter femoral artery flow, glucose uptake, or 1-MX metabolism. Insulin (10 mU·min-1·kg-1) significantly increased hindlimb total blood flow (0.69 ± 0.02 to 1.22 ± 0.11 ml/min, P < 0.05), glucose uptake (0.27 ± 0.05 to 0.95 ± 0.08 μmol/min, P < 0.05), 1-MX uptake (5.0 ± 0.5 to 8.5 ± 1.0 nmol/min, P < 0.05), and skeletal muscle microvascular volume measured by CEU (10.0 ± 1.6 to 15.0 ± 1.2 video intensity units, P < 0.05). Addition of l-NAME to insulin completely blocked the effect of insulin on both total limb flow and microvascular recruitment (measured using either 1-MX or CEU) and blunted glucose uptake by 40% ( P < 0.05). We conclude that insulin specifically recruits flow to the microvasculture in skeletal muscle via a nitric oxide-dependent pathway and that this may be important to insulin's overall action to regulate glucose disposal.

Aerosol deposition in the lung with asymmetric airways obstruction: in vivo observation

1989 ◽  
Vol 67 (6) ◽  
pp. 2579-2585 ◽  
Author(s):  
C. S. Kim ◽  
M. A. Eldridge ◽  
L. Garcia ◽  
A. Wanner
Keyword(s):  
Main Bronchus ◽  
Left Lung ◽  
Aerosol Deposition ◽  
Base Line ◽  
Deposition Pattern ◽  
Before And After ◽  
Airway Obstructions ◽  
L 51 ◽  
The Right

Both the total and regional aerosol deposition were measured in six adult sheep before and after an induction of asymmetric airway obstructions, either by local instillation of carbachol solution (CS, 0.1%) distal to the right main bronchus or inhalation challenge of the right lung with carbachol aerosol (CA, 10 breaths). Total lung deposition was determined by monitoring inert monodisperse aerosols [1.0 micron mass median aerodynamic diam (MMAD)] breath-by-breath, at the mouth, by means of a laser aerosol photometer. Cumulative aerosol deposition over the first five breaths as a percent of the initial aerosol concentration (AD5) was used as a deposition index. Regional deposition pattern was determined by scintigraphic images of sulfur-colloid aerosol (1.5 microns MMAD) tagged with 99mTc. Radioactivity counts in the right (R) and left lung (L) were expressed as a percent of the whole lung count. Half-lung AD5 was then determined by multiplying AD5 by fractional radioaerosol depositions in R or L. Pulmonary airflow resistance (RL mean +/- SE), as determined by an esophageal balloon technique, increased by 111 +/- 28 and 250 +/- 96% after CA and CS, respectively (P less than 0.05). AD5 also increased in all the sheep tested by 29 +/- 3 and 52 +/- 8%, respectively, after CA and CS (P less than 0.05). Radioaerosol deposition pattern was even at base line (R/L = 51:49) but shifted toward the unchallenged L after CS (R/L = 40:60). Deposition pattern after CA was variable: a shift toward L in three, no change in one, and a shift toward the R lung in two sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Cerebral Blood Flow and Brain Oxygenation in Rats Breathing Oxygen under Pressure

2005 ◽  
Vol 25 (10) ◽  
pp. 1288-1300 ◽  
Author(s):  
Ivan T Demchenko ◽  
Yuriy I Luchakov ◽  
Alexander N Moskvin ◽  
Diana R Gutsaeva ◽  
Barry W Allen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Platinum Electrodes ◽  
Brain Oxygenation ◽  
Before And After ◽  
Scatter Plots ◽  
Opposing Effects ◽  
Breathing Room

Hyperbaric oxygen (HBO2) increases oxygen tension (PO2) in blood but reduces blood flow by means of O2-induced vasoconstriction. Here we report the first quantitative evaluation of these opposing effects on tissue PO2 in brain, using anesthetized rats exposed to HBO2 at 2 to 6 atmospheres absolute (ATA). We assessed the contribution of regional cerebral blood flow (rCBF) to brain PO2 as inspired PO2 (PiO2) exceeds 1 ATA. We measured rCBF and local PO2 simultaneously in striatum using collocated platinum electrodes. Cerebral blood flow was computed from H2 clearance curves in vivo and PO2 from electrodes calibrated in vitro, before and after insertion. Arterial PCO2 was controlled, and body temperature, blood pressure, and EEG were monitored. Scatter plots of rCBF versus pO2 were nonlinear ( R2 = 0.75) for rats breathing room air but nearly linear ( R2 = 0.88–0.91) for O2 at 2 to 6 ATA. The contribution of rCBF to brain PO2 was estimated at constant inspired PO2, by increasing rCBF with acetazolamide (AZA) or decreasing it with N-nitro-l-arginine methyl ester (l-NAME). At basal rCBF (78 mL/100 g min), local PO2 increased 7- to 33-fold at 2 to 6 ATA, compared with room air. A doubling of rCBF increased striatal PO2 not quite two-fold in rats breathing room air but 13- to 64-fold in those breathing HBO2 at 2 to 6 ATA. These findings support our hypothesis that HBO2 increases PO2 in brain in direct proportion to rCBF.

scholarly journals Pharmacological Inhibition of Soluble Epoxide Hydrolase Ameliorates Diet-Induced Metabolic Syndrome in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Abishek Iyer ◽  
Kathleen Kauter ◽  
Md. Ashraful Alam ◽  
Sung Hee Hwang ◽  
Christophe Morisseau ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Epoxide Hydrolase ◽  
Therapeutic Potential ◽  
Body Weight Gain ◽  
Oral Treatment ◽  
Soluble Epoxide Hydrolase ◽  
Endothelial Damage ◽  
Metabolic Dysfunction ◽  
Functional Changes

The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral adipose deposition, hyperglycaemia, glucose and insulin intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH) during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment withtrans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndromein vivoincluding glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. The present study describes the pharmacological responses to this selective sEH inhibitor in rats with the signs of diet-induced metabolic syndrome.

Sign in / Sign up

Export Citation Format

Share Document