LYMPHATIC RESEARCH AND BIOLOGY Volume 2, Number 1, 2004 © Mary Ann Liebert, Inc. Effects of Substance P on Mesenteric Lymphatic Contractility in the Rat SANDRA AMERINI, Ph.D., 1 MARINA ZICHE, M.D., 1 STEVEN T. GREINER, D.V.M., 2 and DAVID C. ZAWIEJA, Ph.D. 2 ABSTRACT Background: Substance P (SP) is associated with lymphatic tissue and is a putative mediator of inflammation. The lymph pump is one of the major “safety factors” preventing edema and its activity is altered by inflammatory mediators. The impact of SP on lymphatics was stud- ied in the rat mesentery. Methods and Results: Rats were prepared for in situ lymphatic observation using intravi- tal videomicroscopic techniques. Sections of the small intestine and mesentery were exteri- orized and superfused. Lymphatic diameters were measured and pumping activity was de- termined from the lymphatic diameter tracing. Lymph pump parameters evaluated included diastolic diameter, systolic diameter, contraction frequency, stroke volume, and lymph pump flow. After a control period, the tissues were exposed to SP (10 9 , 10 8 , 10 7 , 10 6 M). SP re- duced both diameters and increased contraction frequency in a concentration-dependent man- ner. SP (1.0 M) produced the following changes (% of control): reductions in diastolic di- ameter (50%), systolic diameter (55%), and stroke volume (63%); a large increase in contraction frequency (661%); and a modest increase in lymph pump flow (44%). SP also stimulated ves- sels that were not contracting phasically to develop typical contraction patterns. Conclusions: Although SP produced a tonic constriction of the lymphatics, lymph pump flow was maintained or slightly elevated via an increase in contraction frequency. SP also in- duced pumping activity in lymphatics that were previously quiescent, thereby further stim- ulating flow. These effects may serve to minimize the formation of edema in face of the in- flammatory edemagenic conditions produced by SP. INTRODUCTION T he lymphatic system plays an important role in the regulation of body fluid homeo- stasis. It is one of the principal systems through which fluids and proteins from the interstitial tissue are returned to the circulating blood and, as such, is thought to be an important factor in the prevention and resolution of edema, 1 one of the cardinal signs of inflammation. Lymph flow is generated, in large part, by the spontaneous contractions of lymph vessels. 2–5 This “active 1 Department of Pharmacology, University of Florence, Florence, Italy; 2 Department of Medical Physiology and Car- diovascular Research Institute Division of Lymphatic Biology, Texas A&M University System Health Science Center, College Station, Texas Grant Support: American Heart Association, National Center Grant-In-Aid 901205; National Heart Lung and Blood Institute Grants HL49601 and HL70308; and the Research Council of Italy 2