scholarly journals Multiscale modeling and simulation of neurovascular coupling in the retina

2018 ◽  
Vol 2 (2) ◽  
pp. 30-35
Author(s):  
Riccardo Sacco ◽  
Aurelio G. Mauri ◽  
Alessandra Cardani ◽  
Brent A. Siesky ◽  
Giovanna Guidoboni ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mathematical Model ◽  
Diabetic Retinopathy ◽  
Multiscale Modeling ◽  
Neurovascular Coupling ◽  
Retinal Arterioles ◽  
Potent Vasodilator ◽  
Simulation Results ◽  
Flicker Light

The role of nitric oxide (NO), usually considered as a potent vasodilator, in regulating retinal neurovascular coupling is still elusive. Measurements of flicker light-induced functional hyperemia (FH) in humans show that an increase of NO levels reduces vasodilation. This evidence has led to conjecture that such an increase may be responsible for suppressing flicker-evoked vasodilation in diabetic retinopathy. In this paper, we propose a mathematical model to theoretically investigate the effect of an increase in neural NO (nNO) on the vasodilation of retinal arterioles. Simulation results indicate that nNO increase may:1. significantly aff ect vasoconstrictive agent production by glial cells; and2. elicit vasoconstriction rather than vasodilation in retinal arterioles.Model predictions seem therefore to support the conjecture that NO increase may be responsible for suppressing flicker-evoked vasodilation in diabetic retinopathy.

scholarly journals A mathematical model for the role of N 2 O 3 in enhancing nitric oxide bioavailability following nitrite infusion

Nitric Oxide ◽  
2016 ◽  
Vol 60 ◽  
pp. 1-9 ◽  
Author(s):  
Yien Liu ◽  
Donald G. Buerk ◽  
Kenneth A. Barbee ◽  
Dov Jaron
Keyword(s):  
Nitric Oxide ◽  
Mathematical Model ◽  
Nitric Oxide Bioavailability

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 Mechanisms Mediating Functional Hyperemia in the Brain

2017 ◽  
Vol 24 (1) ◽  
pp. 73-83 ◽  
Author(s):  
Amy R. Nippert ◽  
Kyle R. Biesecker ◽  
Eric A. Newman
Keyword(s):  
Nitric Oxide ◽  
Arachidonic Acid ◽  
Final Section ◽  
Neurovascular Coupling ◽  
Functional Hyperemia ◽  
Generating Functional ◽  
Signaling Mechanisms ◽  
The Brain ◽  
Astrocyte Endfeet

Neuronal activity within the brain evokes local increases in blood flow, a response termed functional hyperemia. This response ensures that active neurons receive sufficient oxygen and nutrients to maintain tissue function and health. In this review, we discuss the functions of functional hyperemia, the types of vessels that generate the response, and the signaling mechanisms that mediate neurovascular coupling, the communication between neurons and blood vessels. Neurovascular coupling signaling is mediated primarily by the vasoactive metabolites of arachidonic acid (AA), by nitric oxide, and by K+. While much is known about these pathways, many contentious issues remain. We highlight two controversies, the role of glial cell Ca2+ signaling in mediating neurovascular coupling and the importance of capillaries in generating functional hyperemia. We propose signaling pathways that resolve these controversies. In this scheme, capillary dilations are generated by Ca2+ increases in astrocyte endfeet, leading to production of AA metabolites. In contrast, arteriole dilations are generated by Ca2+ increases in neurons, resulting in production of nitric oxide and AA metabolites. Arachidonic acid from neurons also diffuses into astrocyte endfeet where it is converted into additional vasoactive metabolites. While this scheme resolves several discrepancies in the field, many unresolved challenges remain and are discussed in the final section of the review.

Role of 5,6-epoxyeicosatrienoic acid in the regulation of newborn piglet pulmonary vascular tone

2002 ◽  
Vol 283 (2) ◽  
pp. L383-L389 ◽  
Author(s):  
Mamta Fuloria ◽  
Thuy K. Smith ◽  
Judy L. Aschner
Keyword(s):  
Nitric Oxide ◽  
Newborn Piglet ◽  
Epoxyeicosatrienoic Acid ◽  
Resistance Arteries ◽  
Calcium Dependent ◽  
Cox Inhibitor ◽  
Potent Vasodilator ◽  
Oxide Synthase ◽  
Cytochrome P 450

We examined the responses of newborn piglet pulmonary resistance arteries (PRAs) to 5,6-epoxyeicosatrienoic acid (5,6-EET), a cytochrome P-450 metabolite of arachidonic acid. In PRAs preconstricted with a thromboxane A2 mimetic, 5,6-EET caused a concentration-dependent dilation. This dilation was partially inhibited by the combination of charybdotoxin (CTX) and apamin, inhibitors of large and small conductance calcium-dependent potassium (KCa) channels, and was abolished by depolarization of vascular smooth muscle with KCl. Disruption of the endothelium significantly attenuated the dilation, suggesting involvement of one or more endothelium-derived vasodilator pathways in this response. The dilation was partially inhibited by nitro-l-arginine (l-NA), an inhibitor of nitric oxide synthase (NOS), but was unaffected by indomethacin, a cyclooxygenase (COX) inhibitor. The combined inhibition of NOS and KCa channels with l-NA, CTX, and apamin abolished 5,6-EET-mediated dilation. Similarly, combined inhibition of NOS and COX abolished the response. We conclude that 5,6-EET is a potent vasodilator in newborn piglet PRAs. This dilation is mediated by redundant pathways that include release of nitric oxide (NO) and COX metabolites and activation of KCa channels. The endothelium dependence of this response suggests that 5,6-EET is not itself an endothelium-derived hyperpolarizing factor (EDHF) but may induce the release of one or more endothelium-derived relaxing factors, such as NO and/or EDHF.

Reduction of Placental Nitric Oxide Synthase Activity in Pre-Eclampsia

1997 ◽  
Vol 93 (1) ◽  
pp. 51-55 ◽  
Author(s):  
S. P. Brennecke ◽  
N. M. Gude ◽  
J. L. Di Iulio ◽  
R. G. King
Keyword(s):  
Nitric Oxide ◽  
Adverse Effect ◽  
Nitric Oxide Synthase ◽  
Mode Of Delivery ◽  
Placental Tissue ◽  
Potent Vasodilator ◽  
Tissue Homogenates ◽  
Oxide Synthase ◽  
Nitric Oxide Synthase Activity

1. The role of the potent vasodilator nitric oxide in the pathogenesis of pre-eclampsia is unclear. We have tested the hypothesis that placental activity of the enzyme which synthesizes nitric oxide (nitric oxide synthase) is reduced in pre-eclampsia. 2. Placentae were obtained after vaginal delivery or Caesarean section from women who had been assigned to the following groups according to standard obstetric criteria: term non-pre-eclamptic control, term pre-eclamptic, preterm non-pre-eclamptic control and preterm pre-eclamptic. Nitric oxide synthase activity of placental tissue homogenates was assessed by measuring conversion of [3H]l-arginine into [3H]l-citrulline in the presence of NADPH, FAD, tetrahydrobiopterin, calmodulin, CaCl2, magnesium acetate and a range of l-arginine concentrations. Michaelis Menton constants (Km) amd maximum velocities of reaction (Vmax) were calculated using Lineweaver—Burk analysis. 3. Vmax was significantly reduced in both term and preterm pre-eclamptic placentae compared with placentae from corresponding gestation-matched controls. There were no significant differences in the Km values for nitric oxide synthase between any of the four groups, nor were Vmax or Km values significantly influenced by mode of delivery. 4. These results provide evidence that human placental nitric oxide synthase activity is significantly reduced in pre-eclampsia. Such a reduction was evident at both term and preterm gestations. Reduced placental nitric oxide synthase activity may have an adverse effect on placental haemodynamic function in pre-eclampsia, and could be involved in the pathogenesis of this important and common obstetric complication.

scholarly journals Acute retinal ischemia inhibits endothelium‐dependent nitric oxide‐mediated dilation of retinal arterioles: role of endothelin‐1 and superoxide

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Travis W. Hein ◽  
Zhaoxu Yuan ◽  
Wenjuan Xu ◽  
Yi Ren ◽  
Elizabeth Roberts ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Retinal Ischemia ◽  
Endothelin 1 ◽  
Retinal Arterioles
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