Microlymphatic and tissue oxygen tension in the rat mesentery

Hangai-Hoger, Nanae; Cabrales, Pedro; Briceño, Juan Carlos; Tsai, Amy G.; Intaglietta, Marcos

doi:10.1152/ajpheart.00913.2003

Cited by 36 publications

(35 citation statements)

References 15 publications

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“…It should be noted that, because the concentration of NO within the lymphatic vasculature [2,3] is approximately two orders of magnitude lower than that of oxygen [13], the use of a pseudosecond-order reaction rate was employed rather than a third-order term [12]. A sigmoidal relationship between NO production and axial WSS was used as the flux boundary condition [14] for NO production at the wall of the vessel (Eq.…”

Section: à3mentioning

confidence: 99%

Confocal Image-Based Computational Modeling of Nitric Oxide Transport in a Rat Mesenteric Lymphatic Vessel

Wilson

Wang

Hellerstedt

et al. 2013

Journal of Biomechanical Engineering

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The lymphatic system plays important roles in protein and solute transport as well as in the immune system. Its functionality is vital to proper homeostasis and fluid balance. Lymph may be propelled by intrinsic (active) vessel pumping or passive compression from external tissue movement. With regard to the former, nitric oxide (NO) is known to play an important role modulating lymphatic vessel contraction and vasodilation. Lymphatic endothelial cells (LECs) are sensitive to shear, and increases in flow have been shown to cause enhanced production of NO by LECs. Additionally, high concentrations of NO have been experimentally observed in the sinus region of mesenteric lymphatic vessels. A computational flow and mass transfer model using physiologic geometries obtained from confocal images of a rat mesenteric lymphatic vessel was developed to determine the characteristics of NO transport in the lymphatic flow regime. Both steady and unsteady analyses were performed. Production of NO was shear-dependent; basal cases using constant production were also generated. Simulations revealed areas of flow stagnation adjacent to the valve leaflets, suggesting the high concentrations observed here experimentally are due to minimal convection in this region. LEC sensitivity to shear was found to alter the concentration of NO in the vessel, and the convective forces were found to profoundly affect the concentration of NO at a Péclet value greater than approximately 61. The quasisteady analysis was able to resolve wall shear stress within 0.15% of the unsteady case. However, the percent difference between unsteady and quasisteady conditions was higher for NO concentration (6.7%). We have shown high NO concentrations adjacent to the valve leaflets are most likely due to flow-mediated processes rather than differential production by shear-sensitive LECs. Additionally, this model supports experimental findings of shear-dependent production, since removing shear dependence resulted in concentrations that are physiologically counterintuitive. Understanding the transport mechanisms and flow regimes in the lymphatic vasculature could help in the development of therapeutics to treat lymphatic disorders.

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Section: à3mentioning

confidence: 99%

Confocal Image-Based Computational Modeling of Nitric Oxide Transport in a Rat Mesenteric Lymphatic Vessel

Wilson

Wang

Hellerstedt

et al. 2013

Journal of Biomechanical Engineering

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“…The Krebs-bicarbonate solution, in which PO 2 was maintained at 56.7 Ϯ 1.6 mmHg (n ϭ 10) and pH at 7.4 Ϯ 0.01 by bubbling with 5% CO 2-95% N2 (15,(25)(26)(27), was perfused extraluminally over the lymph vessels within the organ chamber. Physiological salt solution with 5% CO 2-95% N2 is also useful for studying lymphatic circulation (2,36,40,49), because PO 2 in the lymphatic circulation is known to be ϳ25-40 mmHg, which is lower than that obtained with blood circulation in physiological conditions (9,16).…”

Section: Methodsmentioning

confidence: 98%

ATP inhibits pump activity of lymph vessels via adenosine A₁ receptor-mediated involvement of NO- and ATP-sensitive K⁺ channels

Kousai¹,

Mizuno²,

Ikomi³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Kousai, Akira, Risuke Mizuno, Fumitaka Ikomi, and Toshio Ohhashi. ATP inhibits pump activity of lymph vessels via adenosine A 1 receptor-mediated involvement of NO-and ATP-sensitive K ϩ channels. Am J Physiol Heart Circ Physiol 287: H2585-H2597, 2004. First published August 12, 2004 doi:10.1152/ajpheart.01080. 2003.-We examined the effects of ATP on intrinsic pump activity in lymph vessels isolated from the rat. ATP caused significant dilation with a cessation of lymphatic pump activity. Removal of the endothelium or pretreatment with N -nitro-L-arginine methyl ester (L-NAME) significantly reduced ATP-induced inhibitory responses of lymphatic pump activity, whereas reduction was not suppressed completely by 10 Ϫ6 M ATP. L-Arginine significantly restored ATPinduced inhibitory responses in the presence of L-NAME. ATPinduced inhibitory responses in lymph vessels with endothelium were also significantly, but not completely, suppressed by pretreatment with glibenclamide. 8-Cyclopentyl-1,3-dipropylxanthine (a selective adenosine A 1 receptor antagonist), but not suramine (a P2X and P2Y receptor antagonist) or 3,7-dimethyl-1-proparglyxanthine (a selective adenosine A 2 receptor antagonist), significantly decreased ATP-induced inhibitory responses. ␣,␤-Methylene ATP (a selective P2X and P2Y receptor agonist) had no significant effect on lymphatic pump activity. In some lymph vessels with endothelium (24 of 30 preparations), adenosine also caused dose-dependent dilation with a cessation of lymphatic pump activity. L-NAME significantly reduced the inhibitory responses induced by the lower (3 ϫ 10 Ϫ8 -3 ϫ 10 Ϫ7 M) concentrations of adenosine. Glibenclamide or 8-cyclopentyl-1,3-dipropylxanthine also significantly suppressed adenosine-induced inhibitory responses. These findings suggest that ATP-induced dilation and inhibition of pump activity of isolated rat lymph vessels are endothelium-dependent and -independent responses. ATP-mediated inhibitory responses may be, in part, related to production of endogenous nitric oxide, involvement of ATP-sensitive K ϩ channels, or activation of adenosine A 1 receptors in lymphatic smooth muscle and endothelium.rat; endothelium; smooth muscle; nitric oxide THE TRANSPORT OF LYMPH depends on passive and active driving forces as well as the rate of lymph production in organs and tissues. The active driving forces, resulting from intrinsic pump activity of lymph vessels, play a pivotal role in the centripetal propulsion of lymph (1,31,39). Neural (21), humoral (30), and mechanical factors (8,22,23) modify the rhythm and amplitude of lymphatic intrinsic pump activity. Recently, it has become clear that lymphatic endothelium-derived nitric oxide (NO) strongly contributes to regulation of lymphatic intrinsic pump activity. Thus NO causes relaxation of lymphatic smooth muscles and reduces lymphatic intrinsic pump activity (24,26,27,35,40,45,48). ATP-sensitive K ϩ (K ATP ) channels have been found in the plasma membrane of cells, including vascular and nonvascular smooth muscles, and then beca...

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“…We also raise some crucial questions to be answered in future research. ported the revelation of these transparent vessels [6] [7] [8] [9]. Table 1 The PVs and PNs are revealed in the connective tissues and blood vessels of the umbilical cord (UC).…”

Section: Introductionmentioning

confidence: 99%

The Integrative Five-Fluid Circulation System in the Human Body

Fung¹,

Kong²

2016

OJMIP

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Water is the key medium to transport numerous constituents and to provide a platform for physiological processes to take place in the living organisms in general; it also participates actively in many of these processes. In humans, there are different vehicles to contain water and its constituents. Our objective is to find out whether there is an overall water-base circulation system in the human body by analyzing the updated findings of different research groups on the physiological functions of various seemingly isolated fluid systems. By 1963, there were five separate fluid systems discovered in mammalians: (i) The Primo Vasculature Fluid (PVF) with protein precursors and micro cells held in the Primo Vasculature System (PVS). (ii) Blood with its constituents held in the cardio vasculature. (iii) Extracranial interstitial fluid (ISF) whose vehicle had a very irregular structure-the interstitium all over the body. (iv) The cerebrospinal fluid had been considered to be within the brain ventricles and spinal canal. (v) The extra-cranial lymphatic system which drained ISF, and had been known to join the subclavian vein. Fluid (i) was first reported in 1963 and fluids (ii) to (v) have been known for many decades, but the failure to detect a lymphatic system inside the skull has also been a mystery for many decades. The intra-cranial ISF (which we name as BISF) has drawn little attention, apart from discussing the mechanism of the blood-brain-barrier. During the past decade, there has been direct evidence indicating that CSF and BISF are actually mixed. After that, the intracranial lymphatic system was discovered and confirmed in animal models only slightly over one year back, and we called such fluid as glymphatic-fluid. After reviewing the stated "classical" five fluid systems together with the new findings in Sections 2 -7, we propose, for the first time, that the PVF, the blood, ISF, a mixture of CSF-BISF, and a mixture of glymphatic-fluid and lymph form an integrative circulation system in water base in the human and other mammalian bodies, as schematically represented in the last section. In this paper, we point out the positive correlation of chronic neuro degenerative diseases such as Alzheimer's disease, Parkinson's diseases and the insufficient brain wastes clearance by the glymphatic system. We also discuss the role played by the venous vessels as part of such clearance in upright posture. Moreover, simple non-invasive maneuver techniques are introduced here, as one example of enhancement of glymphatic fluid flow out of the skull to join the lymphatic system. A series of questions are raised in Section 8, the answers to which would help us to understand the transition from physio-to pathological states in the development of many diseases. Detailed analysis of this paper leads us to consider that research in understanding this integrative circulation system is only at the infancy stage, and fluid dynamics investigation seems to be the plausible modality of approach in the near future.

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Microlymphatic and tissue oxygen tension in the rat mesentery

Cited by 36 publications

References 15 publications

Confocal Image-Based Computational Modeling of Nitric Oxide Transport in a Rat Mesenteric Lymphatic Vessel

Confocal Image-Based Computational Modeling of Nitric Oxide Transport in a Rat Mesenteric Lymphatic Vessel

ATP inhibits pump activity of lymph vessels via adenosine A₁ receptor-mediated involvement of NO- and ATP-sensitive K⁺ channels

The Integrative Five-Fluid Circulation System in the Human Body

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Microlymphatic and tissue oxygen tension in the rat mesentery

Cited by 36 publications

References 15 publications

Confocal Image-Based Computational Modeling of Nitric Oxide Transport in a Rat Mesenteric Lymphatic Vessel

Confocal Image-Based Computational Modeling of Nitric Oxide Transport in a Rat Mesenteric Lymphatic Vessel

ATP inhibits pump activity of lymph vessels via adenosine A1 receptor-mediated involvement of NO- and ATP-sensitive K+ channels

The Integrative Five-Fluid Circulation System in the Human Body

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ATP inhibits pump activity of lymph vessels via adenosine A₁ receptor-mediated involvement of NO- and ATP-sensitive K⁺ channels