An Automated Method to Control Preload by Compensation for Stress Relaxation in Spontaneously Contracting, Isometric Rat Mesenteric Lymphatics

Davis, Michael J.; Lane, Megan M.; Scallan, Joshua P.; Gashev, Anatoliy A.; Zawieja, David C.

doi:10.1080/10739680701436152

Cited by 11 publications

(16 citation statements)

References 14 publications

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“…To precisely control the rate of passive force changes, a servo-controlled piezo stack (Burleigh Inchworm, Fishers, NY) was mounted to a small vessel wire myograph (customized model 310A; Danish Myo Technology, Arhus, Denmark). Stress relaxation of the lymphatic vessel was compensated by the servocontrol of passive force, as described previously (7). The direct output option of the myograph allowed the frequency response of the control loop to be increased to 200 Hz.…”

Section: Methodsmentioning

confidence: 99%

“…In parallel experiments, mesenteric lymphatic segments were cannulated with glass micropipettes and pressurized on the stage of an inverted microscope, while diameter changes were tracked by computer (5). To precisely control the rate of intraluminal pressure changes, another servo-controlled system was developed, similar to that used in previous experiments on arterioles (7). Servo-null style shaker pumps (Ling, Hertz, UK) connected to the pipettes were driven by a hardware-based servo controller through unitary-gain power amplifiers (Cardiovascular Research Institute, Texas A&M University).…”

Section: Methodsmentioning

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: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Modulation of lymphatic muscle contractility by the neuropeptide substance P

Davis¹,

Lane²,

Davis³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

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“…Diameter changes were continuously tracked by computer (7). To control the rate of change in intraluminal pressure (dP/dt), the pipette connections were switched from the reservoir to a servo-controlled pressure system, consisting of a servo-null-style shaker pump driven by a hardware-based servo controller through a unitary-gain power amplifier (15). The controller compared the output signal from a low-pressure transducer (model 104, CyQ, Nicholsville, KY) with a reference voltage specified by a computer and adjusted the pump voltage accordingly.…”

Section: Methodsmentioning

confidence: 99%

“…After equilibration at baseline pressures (0.5, 1, 3, and 5 cmH2O), pressure was stepped by ϩ2, ϩ4, ϩ6, ϩ8, ϩ10, and ϩ12 cmH2O. Values of normalized EDD were then averaged over contractions [15][16][17][18][19][20][21][22][23][24][25] after the pressure step to estimate the steady-state constriction achieved. B: change in diameter plotted as a function of the final pressure for the same vessels and pressure steps in A.…”

Section: Myogenic Constrictionmentioning

confidence: 99%

Myogenic constriction and dilation of isolated lymphatic vessels

Davis¹,

Davis²,

Ku³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Davis MJ, Davis AM, Ku CW, Gashev AA. Myogenic constriction and dilation of isolated lymphatic vessels. Am J Physiol Heart Circ Physiol 296: H293-H302, 2009. First published November 21, 2008 doi:10.1152/ajpheart.01040.2008.-We tested the hypothesis that lymphatics would exhibit myogenic constrictions and dilations to intraluminal pressure changes. Collecting lymphatic vessels were isolated from rat mesentery, cannulated, and pressurized for in vitro study. The lymphatic diameter responses to controlled intraluminal pressure steps of different magnitudes were tested in the absence and presence of the inflammatory mediator substance P, which is known to enhance lymphatic contractility. Myogenic constriction, defined as a time-dependent decrease in end-diastolic diameter over a 1-to 2-min period following pressure elevation (after initial distension), was observed in the majority of rat mesenteric lymphatic vessels in vitro and occurred over a relatively wide pressure range (1-15 cmH 2O). Myogenic dilation, a time-dependent rise in end-diastolic diameter following pressure reduction, was observed in over half the vessels equilibrated at a low baseline pressure. Myogenic constrictions were independent of the cardiac-like and time-dependent compensatory decline in end-systolic diameter and increase in amplitude observed in almost all vessels following pressure elevation. Substance P increased the percentage of vessels exhibiting myogenic constriction, the magnitude and rate of constriction, and the pressure range over which constriction occurred. Our results demonstrate that myogenic responses occur in collecting lymphatic vessels and suggest that the response may aid in preventing vessel overdistension during inflammation/edema.

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“…Though lymphatic vessels generate the least active tension and stress among these three vessels, the lymphatic vessels exhibited distinct elastic characteristics, as well as both phasic and tonic contractions (4,48,49). Because tonic and phasic smooth muscle myofilaments exhibit different biochemical characteristics and the lymphatic muscle has unique biomechanical properties, we hypothesized that the calcium sensitivity and cooperativity of lymphatic myofilaments must be different from tonic vascular smooth muscle to attain its unique phasic and tonic contractile nature.…”

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confidence: 99%