Modulation of lymphatic muscle contractility by the neuropeptide substance P

• Published in: American journal of physiology. Heart and circulatory physiology 2008-08, Vol.295 (2), p.H587-H597
• Main Authors: Davis, Michael J, Lane, Megan M, Davis, Ann M, Durtschi, David, Zawieja, David C, Muthuchamy, Mariappan, Gashev, Anatoliy A
• Format: Article
• Language: English
• Subjects: Animals; In Vitro Techniques; Isometric Contraction; Lymphatic system; Lymphatic Vessels - metabolism; Male; Muscles - metabolism; Myography; Peptides; Pressure; Rats; Rats, Sprague-Dawley; Rodents; Studies; Substance P - metabolism; Time Factors
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01029.2007

1 Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri; and 2 Department 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 PLA 2 inhibition. In the absence of SP, ramp increases in isometric preload resulted in x 1.6 increases in contraction amplitude (Amp) and x 1.7 increases in frequency (Freq). SP increased Freq by x 2.4, Amp by x 1.9, and the Amp-Freq product (AFP) by x 3.5. Under isobaric conditions, the pressure elevation from 0.5 to 10 cmH 2 O in the absence of SP decreased Amp by x 0.6 and increased Freq by x 1.8. 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 A 2 Address for reprint requests and other correspondence: M. J. Davis, Dept. of Medical Pharmacology and Physiology, Univ. of Missouri School of Medicine, 1 Hospital Dr., Rm. M451, Columbia, MO 65212 (e-mail: davismj{at}health.missouri.edu )