Length‐Dependence of Lymphatic Phasic Contractile Activity Under Isometric and Isobaric Conditions

Zhang, Rongzhen; Gashev, Anatoliy A.; Zawieja, David C.; Lane, Megan M.; Davis, Michael J.

doi:10.1080/10739680701436160

Cited by 39 publications

(50 citation statements)

References 52 publications

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“…Figure 3 shows the response of a representative isometric lymphatic vessel to two successive ramp increases in preload from 0.02 to 1.0 mN, spanning the range of stretch (pressure) normally experienced by similar vessels in vivo under normal conditions and during edemagenic stress (3). The advantage of using a continuous preload ramp over a series of preload steps is that this procedure allowed the measurement of the essentially continuous relationships between preload and the various lymphatic contraction parameters over a relatively short time interval (51). The raw data for two successive preload ramps are shown in (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The effects of preload on the spontaneous contraction patterns of isometric rat mesenteric lymphatics have been described recently (51). The servo-control system could generate constant speed, ramp increases in passive force to generate essentially continuous relationships between preload and either Amp, frequency (Freq), or their product [Amp-Freq product (AFP)] and then to assess the effects of SP on those relationships.…”

Section: Methodsmentioning

confidence: 99%

“…A slow preload ramp up to 1.0 mN was then imposed over a time course of ϳ9 min. These parameters permitted the acquisition of a sufficient number of spontaneous contractions (for subsequent data analysis) over a range of preloads equivalent to the physiological range of pressures normally experienced by these vessels in vivo (11,51). Fresh, preheated APSS was then exchanged for the bath solution, the force transducer was rezeroed, and the preload was again set to 0.02 mN.…”

Section: Methodsmentioning

confidence: 99%

“…We used isolated, cannulated lymphatic vessels to distinguish between the possible direct and indirect actions of SP as defined above. We used rat mesenteric vessels because of the extensive amount of available data regarding the contractile behavior of these vessels both in vivo (2, 3, 49) and in vitro (11,12,51). A unique aspect of our study was to assess the action of SP on collecting lymphatic vessels under both isometric and isobaric conditions.…”

mentioning

confidence: 99%

“…These vascular effects of SP would collectively increase flow/ pressure in capillaries and post-capillary venules and lead to increases in transcapillary fluid flux. The resulting increases in interstitial fluid volume and interstitial fluid pressure would enhance lymph formation (42, 43) and stimulate lymphatic pump activity through the well-described relationship of lymphatic filling pressure on lymphatic pumping (11,34,51).…”

mentioning

confidence: 99%

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Modulation of lymphatic muscle contractility by the neuropeptide substance P

Davis¹,

Lane²,

Davis³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Davis MJ, Lane MM, Davis AM, Durtschi D, Zawieja DC, Muthuchamy M, Gashev AA. Modulation of lymphatic muscle contractility by the neuropeptide substance P. Am J Physiol Heart Circ Physiol 295: H587-H597, 2008. First published June 6, 2008 doi:10.1152/ajpheart.01029.2007.-Substance P (SP) is a neuropeptide associated with sensory innervation of lymphoid tissue and a suspected modulator of lymphatic function in inflammation. Only a few studies have examined the effects of SP on lymphatic contraction, and it is not clear to what extent SP acts directly on the lymphatic muscle and/or endothelium or indirectly through changes in intraluminal filling pressure secondary to increases in capillary permeability/ filtration. We tested the effects of SP on the spontaneous contractions of rat isolated mesenteric lymphatic vessels under isometric and isobaric conditions, hypothesizing that low concentrations would stimulate lymphatic pumping by enhancing lymphatic muscle contraction in a manner complementary to the effect of increased preload. Under isometric conditions, SP (10 nM) dramatically enhanced lymphatic chronotropy and inotropy. Unlike guinea pig lymphatics, SP actions were not blocked by cyclooxygenase or PLA2 inhibition. In the absence of SP, ramp increases in isometric preload resulted in ϫϳ1.6 increases in contraction amplitude (Amp) and ϫϳ1.7 increases in frequency (Freq). SP increased Freq by ϫϳ2.4, Amp by ϫϳ1.9, and the Amp-Freq product (AFP) by ϫϳ3.5. Under isobaric conditions, the pressure elevation from 0.5 to 10 cmH2O in the absence of SP decreased Amp by ϫϳ0.6 and increased Freq by ϫϳ1.8. SP caused a modest increase in Amp, a robust increase in Freq at all pressures, and shifted the AFP-pressure relationship upward and leftward. Therefore, SP has substantial positive inotropic and chronotropic effects on rat lymphatic muscle, improving pump efficiency independent of the effects of preload and broadening of the working range of the lymphatic pump. neurokinin; edema; inflammation; lymphatic pump; inotropy; chronotropy; thromboxane A2 SUBSTANCE P (SP) is an 11-amino acid neuropeptide (36) often associated with cells of lymphoid tissue (15,19,21,22,46,47). SP is released from enteric nerves, sensory nerves, and inflammatory cells (27,41,45,52). Correspondingly, SP receptors are expressed on endothelium and muscle of blood and lymphatic vessels, on nerves innervating those vessels, and on associated immune and inflammatory cells (31,36,44).SP appears to have both direct and indirect effects on vascular targets. For example, SP is a powerful stimulator of endothelium-dependent nitric oxide production (28), evoking vasodilation and increasing local blood flow. In addition, SP enhances vascular permeability (18,25) and stimulates the release of cytokines and chemokines (4, 36) that would indirectly elicit vasodilation and increase vascular permeability. These vascular effects of SP would collectively increase flow/ pressure in capillaries and post-capillary venules and lead to increases in transcapillary fluid ...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Modulation of lymphatic muscle contractility by the neuropeptide substance P

Davis¹,

Lane²,

Davis³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Lymphatic Vessel Network Structure and Physiology

Breslin

Yang

Scallan

et al. 2018

Comprehensive Physiology

272

258

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The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic environment for every cell in all tissues of the body. The lymphatic system maintains extracellular fluid homeostasis favorable for optimal tissue function, removing substances that arise due to metabolism or cell death, and optimizing immunity against bacteria, viruses, parasites, and other antigens. This article provides a comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease.

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