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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/H587    most recent 01029.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Davis, M. J. Articles by Gashev, A. A. PubMed PubMed Citation Articles by Davis, M. J. Articles by Gashev, A. A.

Modulation of lymphatic muscle contractility by the neuropeptide substance P

¹Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri; and ²Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Division of Lymphatic Biology, Texas A&M Health Science Center, Temple, Texas

Submitted 5 September 2007 ; accepted in final form 22 May 2008

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 x1.6 increases in contraction amplitude (Amp) and x1.7 increases in frequency (Freq). SP increased Freq by x2.4, Amp by x1.9, and the Amp-Freq product (AFP) by x3.5. Under isobaric conditions, the pressure elevation from 0.5 to 10 cmH₂O in the absence of SP decreased Amp by x0.6 and increased Freq by x1.8. 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

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