S-nitroso-albumin carries a thiol-labile pool of nitric oxide, which causes venodilation in the rat

2005 ◽  
Vol 289 (2) ◽  
pp. H916-H923 ◽  
Author(s):  
Nelson N. Orie ◽  
Patrick Vallance ◽  
Dean P. Jones ◽  
Kevin P. Moore
Keyword(s):  
Nitric Oxide ◽  
Molecular Weight ◽  
Blood Flow ◽  
Vascular Function ◽  
Low Molecular Weight ◽  
Aortic Blood Flow ◽  
Hemodynamic Effects ◽  
Rapid Decomposition ◽  
Aortic Blood

It is now established that S-nitroso-albumin (SNO-albumin) circulates at low nanomolar concentrations under physiological conditions, but concentrations may increase to micromolar levels during disease states (e.g., cirrhosis or endotoxemia). This study tested the hypothesis that high concentrations of SNO-albumin observed in some diseases modulate vascular function and that it acts as a stable reservoir of nitric oxide (NO), releasing this molecule when the concentrations of low-molecular-weight thiols are increased. SNO-albumin was infused into rats to increase the plasma concentration from <50 nmol/l to ∼4 μmol/l. This caused a 29 ± 6% drop in blood pressure, 20 ± 4% decrease in aortic blood flow, and a 25 ± 14% reduction of renal blood flow within 10 min. These observations were in striking contrast to those of an infused arterial vasodilator (hydralazine), which increased aortic blood flow, and suggested that SNO-albumin acts primarily as a venodilator in vivo. This was confirmed by the observations that glyceryl trinitrate (a venodilator) led to similar hemodynamic changes and that the hemodynamic effects of SNO-albumin are reversed by infusion of colloid. Infusion of N-acetylcysteine into animals with artificially elevated plasma SNO-albumin concentrations led to the rapid decomposition of SNO-albumin in vivo and reproduced the hemodynamic effects of SNO-albumin infusion. These data demonstrate that SNO-albumin acts primarily as a venodilator in vivo and represents a stable reservoir of NO that can release NO when the concentrations of low-molecular-weight thiols are elevated.

scholarly journals Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure

2015 ◽  
Vol 309 (11) ◽  
pp. E915-E924 ◽  
Author(s):  
Il-Young Kim ◽  
Scott E. Schutzler ◽  
Amy Schrader ◽  
Horace J. Spencer ◽  
Gohar Azhar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Older Adults ◽  
Blood Flow ◽  
Young Adults ◽  
Vascular Function ◽  
De Novo ◽  
Synthesis Rate ◽  
Fasted State

To determine if age-associated vascular dysfunction in older adults with heart failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed two separate studies: 1) a kinetic study with a stable isotope tracer method to determine in vivo kinetics of NO metabolism, and 2) a vascular function study using a plethysmography method to determine reactive hyperemic forearm blood flow (RH-FBF) in older and young adults in the fasted state and in response to citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was ∼50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citrulline ingestion (3 g) stimulated de novo arginine synthesis in both older [6.88 ± 0.83 to 35.40 ± 4.90 μmol·kg body wt−1·h−1] and to a greater extent in young adults (12.02 ± 1.01 to 66.26 ± 4.79 μmol·kg body wt−1·h−1). NO synthesis rate increased correspondingly in older (0.17 ± 0.01 to 2.12 ± 0.36 μmol·kg body wt−1·h−1) and to a greater extent in young adults (0.36 ± 0.04 to 3.57 ± 0.47 μmol·kg body wt−1·h−1). Consistent with the kinetic data, RH-FBF in the fasted state was ∼40% reduced in older vs. young adults. However, citrulline ingestion (10 g) failed to increase RH-FBF in either older or young adults. In conclusion, citrulline ingestion improved impaired NO synthesis in older HF adults but not RH-FBF, suggesting that factors other than NO synthesis play a role in the impaired RH-FBF in older HF adults, and/or it may require a longer duration of supplementation to be effective in improving RH-FBF.

scholarly journals In vivo transfer of nitric oxide between a plasma protein-bound reservoir and low molecular weight thiols.

1994 ◽  
Vol 94 (4) ◽  
pp. 1432-1439 ◽  
Author(s):  
J S Scharfstein ◽  
J F Keaney ◽  
A Slivka ◽  
G N Welch ◽  
J A Vita ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Molecular Weight ◽  
Plasma Protein ◽  
Low Molecular Weight

Abstract 1138: Endogenous Adipocyte-Derived Factors Diminish Coronary Endothelial-Dependent Vasodilation Via Inhibition Of Nitric Oxide Synthase

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Gregory A Payne ◽  
Lena Borbouse ◽  
Gregory M Dick ◽  
Johnathan D Tune
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Coronary Blood Flow ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Dependent Manner ◽  
Pericardial Adipose Tissue ◽  
Oxide Synthase

Adipocytokines may be the molecular link between obesity and vascular disease; however, effects of these factors on coronary vascular function have not been delineated. Accordingly, this study was designed to examine mechanisms by which endogenous adipocyte-derived factors impair coronary endothelial-dependent vasodilation in vivo . Experiments were conducted in open-chest anesthetized dogs (n = 16) before and during treatment with endogenous adipocyte-derived factors. Phosphate buffered saline was conditioned in a shaking water bath with parietal pericardial adipose tissue (3 g/ml) for 30 min at 37°C. The conditioned buffer was then filtered (0.2 μm) and infused directly into the coronary circulation (0.3 ml/min). Conditioned buffer did not significantly affect baseline coronary blood flow (0.50 ± 0.01 vs. 0.61 ± 0.05 ml/min/g, p = 0.68), mean arterial pressure (103 ± 6 vs. 96 ± 9 mmHg, p = 0.74), or heart rate (87 ± 13 vs. 110 ± 24 beats/min, p = 0.44). Conditioned buffer had no effect on responses to intracoronary angiotensin II (2.5 – 750 ng; 74 vs. 70% vasoconstriction). Under control conditions, bradykinin (0.03 – 3 μg/min) increased coronary blood flow (303 ± 65%) to 2.02 ± 0.31 ml/min/g in a dose-dependent manner. Conditioned buffer attenuated maximum bradykinin vasodilation to 1.64 ± 0.26 ml/min/g (167 ± 33% increase; p < 0.05). This decrease in endothelial-dependent dilation was not due to increases in superoxide production, as administration of the superoxide dismutase mimetic Tempol (10 mg/min, ic) did not improve bradykinin vasodilation (120 ± 27% increase; p < 0.05). Inhibition of nitric oxide synthase with L-NAME (150 μg/min, ic) reduced maximum bradykinin vasodilation to 0.93 ± 0.04 ml/min/g (p < 0.05) and endogenous adipocyte-derived factors had no further inhibitory effect (0.82 ± 0.09 ml/min/g, p = 0.24). These data indicate that endogenous adipocyte-derived factors diminish endothelial-dependent coronary vasodilation via inhibition of nitric oxide synthase rather than a reduction in nitric oxide bioavailability by superoxide. Our findings importantly link endogenous adipocyte-derived factors with pro-atherogenic coronary vascular dysfunction in vivo .

scholarly journals Vasorelaxant and Hypotensive Effects of Jaboticaba Fruit (Myrciaria cauliflora) Extract in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Daniela Medeiros Lobo de Andrade ◽  
Carolina de Fátima Reis ◽  
Patrícia Ferreira da Silva Castro ◽  
Leonardo Luiz Borges ◽  
Nathalia Oda Amaral ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Femoral Vein ◽  
Soluble Guanylyl Cyclase ◽  
Aortic Blood Flow ◽  
Aortic Blood ◽  
Cox Inhibitor

This study’s aim was to determine the effect of hydroalcoholic extract ofM. cauliflora(HEMC) on vascular tension and blood pressure in rats. In ourin vitrostudies using precontracted isolated aortas from rats, HEMC and acetylcholine (positive control) induced relaxation only in vessels with endothelium. Pretreatment with L-NAME (NO synthase inhibitor) or ODQ (soluble guanylyl cyclase (sGC) inhibitor) abolished the HEMC-induced relaxation. The treatment with MDL-12,330A (adenylyl cyclase (AC) inhibitor) or diclofenac (COX inhibitor) reduced HEMC-induced vasorelaxation. The blockade of muscarinic andβ-adrenergic receptors (by atropine and propranolol, resp.) did not promote changes in HEMC-induced vasorelaxation. In ourin vivostudies, catheters were inserted into the right femoral vein and artery of anesthetized rats for HEMC infusion and the measurement of blood pressure, heart rate, and aortic blood flow. The intravenous infusion of HEMC produced hypotension and increased aortic blood flow with no changes in heart rate. These findings showed that HEMC induces endothelium-dependent vascular relaxation and hypotension with no alteration in heart rate. The NO/sGC/cGMP pathway seems to be the main cellular route involved in the vascular responsiveness.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

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