Nitric oxide increases fluid extravasation from the splenic circulation of the rat

2001 ◽  
Vol 280 (4) ◽  
pp. R959-R967 ◽  
Author(s):  
Peter S. Andrew ◽  
Yiming Deng ◽  
Richard Sultanian ◽  
Susan Kaufman
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Lymphatic System ◽  
Resistance Arteries ◽  
No Donor ◽  
Fluid Extravasation ◽  
Resistance Vessels ◽  
Blood Inflow ◽  
The Difference ◽  
Arteries And Veins

We hypothesized that nitric oxide (NO) contributes to intrasplenic fluid extravasation by inducing greater relaxation in splenic resistance arteries than veins such that intrasplenic microvascular pressure (PC) rises. Fluid efflux was estimated by measuring the difference between splenic blood inflow and outflow. Intrasplenic infusion of the NO donor S-nitroso- N-acetylpenicillamine (SNAP) (0.3 μg · 10 μl−1 · min−1) caused a significant increase in intrasplenic fluid efflux (baseline: 0.8 ± 0.4 ml/min, n = 10 vs. peak rise during SNAP infusion: 1.3 ± 0.4 ml/min, n = 10; P < 0.05). Intrasplenic PC was measured in the isolated, blood-perfused rat spleen. Intrasplenic infusion of SNAP (0.1 μg · 10 μl−1 · min−1) caused a significant increase in PC (saline: 10.9 ± 0.2 mmHg, n = 3 vs. SNAP: 12.2 ± 0.2 mmHg, n = 3; P < 0.05). Vasoreactivity of preconstricted splenic resistance vessels to sodium nitroprusside (SNP) (1 × 10−12-1 × 10−4 M) and SNAP (1 × 10−10-3 × 10−4 M) was investigated with the use of a wire myograph system. Significantly greater relaxation of arterioles than of venules occurred with both SNP (%maximal vasorelaxation: artery 96 ± 2.3, n = 9 vs. vein 26 ± 1.9, n = 10) and SNAP (%maximal vasorelaxation: artery 50 ± 3.5, n = 11 vs. vein 32 ± 1.7, n = 8). These results are consistent with our proposal that differential vasoreactivity of splenic resistance arteries and veins to NO elevates intrasplenic PC and increases fluid extravasation into the systemic lymphatic system.

Abnormalities of the lymphatic system and impaired fluid clearance in patients with heart failure with preserved ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Rossitto ◽  
S Mary ◽  
C McAllister ◽  
K.B Neves ◽  
L Haddow ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Blood Vessels ◽  
Lymphatic System ◽  
Filtration Coefficient ◽  
Funding Source ◽  
Preserved Ejection Fraction ◽  
Resistance Arteries ◽  
Fluid Extravasation ◽  
Capillary Fluid

Abstract Background Coronary and skeletal muscle microvascular dysfunction have been proposed as main factors in the pathogenesis of Heart Failure with Preserved Ejection Fraction (HFpEF). However, assessment of systemic arterial function has only been indirect thus far; most importantly, no direct link between systemic microvasculature and congestion, one of the core characteristics of the syndrome, has yet been investigated. Purpose To provide direct functional and anatomical characterisation of the systemic microvasculature and to explore in vivo parameters of capillary fluid extravasation and lymphatic clearance in HFpEF. Methods In 16 patients with HFpEF and 16 age- and sex-matched healthy controls (72±6 and 68±5 years, respectively) we determined peripheral microvascular filtration coefficient (proportional to vascular permeability and area) and isovolumetric pressure (above which lymphatic drainage cannot compensate for fluid extravasation) by venous occlusion plethysmography and collected a skin biopsy for vascular immunohistochemistry and gene expression analysis (TaqMan). Additionally, we measured brachial flow-mediated dilatation (FMD) and assessed by wire myography the vascular function of resistance arteries isolated from gluteal subcutaneous fat biopsies. Results Skin biopsies in patients with HFpEF showed rarefaction of small blood vessels (82±31 vs 112±21 vessels/mm2; p=0.003) and in ex-vivo analysis (n=6/group) we found defective relaxation of peripheral resistance arteries (p&lt;0.001). Accordingly, post-ischaemic hyperaemic response (fold-change vs baseline, 4.6±1.6 vs 6.7±1.7; p=0.002) and FMD (3.9±2.1 vs 5.6±1.5%; p=0.014) were found to be reduced in patients with HFpEF compared to controls. In the skin of patients with HFpEF we also observed a reduced number (85±27 vs 130±60 vessels/mm2; p=0.012) but larger average diameter of lymphatic vessels (42±19 vs 26±9 μm2; p=0.007) compared to control subjects. These changes were paralleled by reduced expression of LYVE1 (p&lt;0.05) and PROX1 (p&lt;0.001), key determinants of lymphatic differentiation and function. Whilst patients with HFpEF had reduced peripheral capillary fluid extravasation compared to controls (microvascular filtration coefficient, leg 33.1±13.3 vs 48.4±15.2, p&lt;0.01; trend for arm 49.9±20.5 vs 66.3±30.1, p=0.09), they had lower lymphatic clearance (isovolumetric pressure: leg 22±4 vs 16±4 mmHg, p&lt;0.005; arm 25±5 vs 17±4 mmHg, p&lt;0.001). Conclusions We provide direct evidence of systemic dysfunction and rarefaction of small blood vessels in patients with HFpEF. Despite a reduced microvascular filtration coefficient, which is in keeping with microvascular rarefaction, the clearance of extravasated fluid in HFpEF is limited by an anatomically and functionally defective lymphatic system. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation Centre of Research Excellence Award

Abstract 16720: Cytoglobin Regulates Cardiovascular Function and Vessel Tone by Controlling the Rate of Vascular Nitric Oxide Metabolism

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Xiaoping Liu ◽  
Mohamed A El-Mahdy ◽  
Raed S Ismail ◽  
Sean Little ◽  
Le T Thuy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Wall ◽  
No Donor ◽  
Nitric Oxide Metabolism ◽  
No Consumption ◽  
Potent Vasodilator ◽  
Inner Diameter ◽  
The Difference ◽  
Synthase Inhibitor

Cytoglobin (Cygb) can effectively metabolize nitric oxide (NO), a potent vasodilator, in the presence of oxygen and reductants. Cygb in the vascular wall may affect cardiovascular functions by changing the rate of NO metabolism. In this study, we directly tested the vascular role of Cygb using Cygb knockout (Cygb-/-) mice. The mean blood pressure of Cygb-/- and C57BL/6 wild type (WT) mice was 65.3 ± 1.9 mmHg and 93.7 ± 1.5 mmHg, respectively (n=10). Using echocardiography, we observed that cardiac output (CO) was increased in Cygb-/- mice compared to WT with values of 29.8 ± 3.9 vs 17.7 ± 0.9 ml/min. The systemic vascular resistance (SVR) of Cygb-/- mice was decreased by ~60% vs that of WT mice (Fig. 1). Further, the inner diameter (id) of aorta of Cygb-/- mice was dilated compared to WT with values of 2.2 ± 0.1 mm vs 1.5 ± 0.05 mm (n=5), respectively. After treatment with the NO synthase inhibitor L-NAME, no difference in the aortic id remained between Cygb-/- (1.55 ± 0.03 mm) and WT (1.49 ± 0.02 mm) mice, indicating that the NO pathway is responsible for the difference in vascular inner diameters and tone. Myograph experiments show that the aortic vasodilation response of Cygb-/- mice is much more sensitive to acetylcholine (Ach) or the NO donor nitroprusside (SNP) (EC50 shifts from 13 nM and 2.9 nM (WT mice) to 0.33 nM and 0.16 nM (Cygb-/-) for Ach and SNP, respectively). Using NO electrodes to measure the rate of NO consumption by SMCs and quantitative imunoblotting to estimate Cygb content in RSMCs-AR and Cygb knockdown RSMCs, we observed that 90% of NO consumption by RSMCs-AR is caused by the intracellular Cygb. Our results indicate that Cygb deficiency in the vascular wall of Cygb-/- mice greatly reduces the rate of NO metabolism and increases vascular NO concentration, resulting in vasodilation, increase in vessel lumen diameter, and decrease in SVR. These results demonstrate that Cygb regulates cardiac function and vessel tone by controlling the rate of vascular NO metabolism.

scholarly journals Complex interactions of NO/cGMP/PKG systems on Ca2+ signaling in afferent arteriolar vascular smooth muscle

2010 ◽  
Vol 298 (1) ◽  
pp. H144-H151 ◽  
Author(s):  
Susan K. Fellner ◽  
William J. Arendshorst
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
No Production ◽  
No Donor ◽  
Complex Interactions ◽  
Resistance Vessels ◽  
Microsphere Method ◽  
Afferent Arterioles ◽  
Oxide Synthase

Little is known about the effects of nitric oxide (NO) and the cyclic GMP (cGMP)/protein kinase G (PKG) system on Ca2+ signaling in vascular smooth muscle cells (VSMC) of resistance vessels in general and afferent arterioles in particular. We tested the hypotheses that cGMP-, Ca2+-dependent big potassium channels (BKCa2+) buffer the Ca2+ response to depolarization by high extracellular KCl and that NO inhibits adenosine diphosphoribose (ADPR) cyclase, thereby reducing the Ca2+-induced Ca2+ release. We isolated rat afferent arterioles, utilizing the magnetized microsphere method, and measured cytosolic Ca2+ concentration ([Ca2+]i) with fura-2, a preparation in which endothelial cells do not participate in [Ca2+]i responses. KCl (50 mM)-induced depolarization causes an immediate increase in [Ca2+]i of 151 nM. The blockers Nω-nitro-l-arginine methyl ester (of nitric oxide synthase), 1,2,4-oxodiazolo-[4,3- a]quinoxalin-1-one (ODQ, of guanylyl cyclase), KT-5823 (of PKG activation), and iberiotoxin (IBX, of BKCa2+ activity) do not alter the [Ca2+]i response to KCl, suggesting no discernible endogenous NO production under basal conditions. The NO donor sodium nitroprusside (SNP) reduces the [Ca2+]i response to 77 nM; IBX restores the response to control values. These data show that activation of BKCa2+ in the presence of NO/cGMP provides a brake on KCl-induced [Ca2+]i responses. Experiments with the inhibitor of cyclic ADPR 8-bromo-cyclic ADPR (8-Br-cADPR) and SNP + downstream inhibitors of PKG and BKCa2+ suggest that NO inhibits ADPR cyclase in intact arterioles. When we pretreat afferent arterioles with 8-bromoguanosine 3′,5′-cyclic monophosphate (8-Br-cGMP; 10 μM), the response to KCl is 143 nM. However, in the presence of both IBX and 8-Br-cGMP, we observe a surprising doubling of the [Ca2+]i response to KCl. In summary, we present evidence for effects of the NO/cGMP/PKG system to reduce [Ca2+]i, via activation of BKCa2+ and possibly by inhibition of ADPR cyclase, and to increase [Ca2+]i, by a mechanism(s) yet to be defined.

scholarly journals Sodium nitroprusside prevents the detrimental effects of glucose on the neurovascular unit and behaviour in zebrafish

2019 ◽  
Author(s):  
K. Chhabria ◽  
A. Vouros ◽  
C. Gray ◽  
R.B. MacDonald ◽  
Z. Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Optic Tectum ◽  
Neurovascular Unit ◽  
Cell Number ◽  
Neuronal Activation ◽  
Negative Effects ◽  
Mural Cell ◽  
No Donor ◽  
Glucose Exposure

AbstractDiabetes is associated with dysfunction of the neurovascular unit, although the mechanisms of this are incompletely understood, and currently no treatment exists to prevent these negative effects. We previously found that the NO donor sodium nitroprusside (SNP) prevents the detrimental effect of glucose on neurovascular coupling in zebrafish. We therefore sought to establish the wider effects of glucose exposure on both the neurovascular unit and on behaviour in zebrafish and the ability of SNP to prevent these.We incubated 4 days post fertilisation (dpf) zebrafish embryos in 20mM glucose or mannitol for five days until 9dpf, with or without 0.1mM SNP co-treatment for 24h (8-9dpf), and quantified vascular nitric oxide reactivity, vascular mural cell number, expression of aklf2areporter, glial fibrillary acidic protein (GFAP) and TRPV4, as well as spontaneous neuronal activation at 9dpf, all in the optic tectum. We also assessed the effect on light/dark preference and locomotory characteristics during free-swimming studies.We find that glucose exposure significantly reduced nitric oxide reactivity,klf2areporter expression, vascular mural cell number and TRPV4 expression, while significantly increasing spontaneous neuronal activation and GFAP expression (all in the optic tectum). Furthermore, when we examined larval behaviour we found glucose exposure significantly altered light/dark preference and high and low speed locomotion while in light. Co-treatment with SNP reversed all these molecular and behavioural effects of glucose exposure.Our findings comprehensively describe the negative effects of glucose exposure on the vascular anatomy, molecular phenotype, and function of the optic tectum and on whole organism behaviour. We also show that SNP or other NO donors may represent a therapeutic strategy to ameliorate the complications of diabetes on the neurovascular unit.

scholarly journals Polyamine Induction in Postharvest Banana Fruits in Response to NO Donor SNP Occurs via l-Arginine Mediated Pathway and Not via Competitive Diversion of S-Adenosyl-l-Methionine

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 358 ◽  
Author(s):  
Veeresh Lokesh ◽  
Girigowda Manjunatha ◽  
Namratha S. Hegde ◽  
Mallesham Bulle ◽  
Bijesh Puthusseri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Arginine Decarboxylase ◽  
No Donor ◽  
Expression Studies ◽  
Common Precursor ◽  
Competitive Action ◽  
Gene Expression Studies

Nitric oxide (NO) is known to antagonize ethylene by various mechanisms; one of such mechanisms is reducing ethylene levels by competitive action on S-adenosyl-L-methionine (SAM)—a common precursor for both ethylene and polyamines (PAs) biosynthesis. In order to investigate whether this mechanism of SAM pool diversion by NO occur towards PAs biosynthesis in banana, we studied the effect of NO on alterations in the levels of PAs, which in turn modulate ethylene levels during ripening. In response to NO donor sodium nitroprusside (SNP) treatment, all three major PAs viz. putrescine, spermidine and spermine were induced in control as well as ethylene pre-treated banana fruits. However, the gene expression studies in two popular banana varieties of diverse genomes, Nanjanagudu rasabale (NR; AAB genome) and Cavendish (CAV; AAA genome) revealed the downregulation of SAM decarboxylase, an intermediate gene involved in ethylene and PA pathway after the fifth day of NO donor SNP treatment, suggesting that ethylene and PA pathways do not compete for SAM. Interestingly, arginine decarboxylase belonging to arginine-mediated route of PA biosynthesis was upregulated several folds in response to the SNP treatment. These observations revealed that NO induces PAs via l-arginine-mediated route and not via diversion of SAM pool.

Acute and repeated exposure with the nitric oxide (NO) donor sodium nitroprusside (SNP) differentially modulate responses in a rat model of anxiety

Nitric Oxide ◽  
2017 ◽  
Vol 69 ◽  
pp. 56-60 ◽  
Author(s):  
Martha A. Orfanidou ◽  
Anastasios Lafioniatis ◽  
Aikaterini Trevlopoulou ◽  
Ntilara Touzlatzi ◽  
Nikolaos Pitsikas
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Rat Model ◽  
Repeated Exposure ◽  
No Donor

scholarly journals The Nitric Oxide (NO) Donor Sodium Nitroprusside (SNP) and Its Potential for the Schizophrenia Therapy: Lights and Shadows

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3196
Author(s):  
Elli Zoupa ◽  
Nikolaos Pitsikas
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Mental Disease ◽  
No Production ◽  
No Donor ◽  
No Donors ◽  
Worldwide Population ◽  
The Brain

Schizophrenia is a severe psychiatric disorder affecting up to 1% of the worldwide population. Available therapy presents different limits comprising lack of efficiency in attenuating negative symptoms and cognitive deficits, typical features of schizophrenia and severe side effects. There is pressing requirement, therefore, to develop novel neuroleptics with higher efficacy and safety. Nitric oxide (NO), an intra- and inter-cellular messenger in the brain, appears to be implicated in the pathogenesis of schizophrenia. In particular, underproduction of this gaseous molecule is associated to this mental disease. The latter suggests that increment of nitrergic activity might be of utility for the medication of schizophrenia. Based on the above, molecules able to enhance NO production, as are NO donors, might represent a class of compounds candidates. Sodium nitroprusside (SNP) is a NO donor and is proposed as a promising novel compound for the treatment of schizophrenia. In the present review, we intended to critically assess advances in research of SNP for the therapy of schizophrenia and discuss its potential superiority over currently used neuroleptics.

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