Uniformed Services University of the Health Sciences
4301 Jones Bridge Road
Bethesda, Maryland 20814
Although this laboratory addresses multiple aspects of both the normal physiology of the cardiovascular system and pathophysiology perturbations in this system. The principal focus of the laboratory is centered in the microcirculation. One avenue of current experimentation delves into the mechanisms of increased microvascular permeability to macro molecules, subsequent edema formation and potential therapeutic approaches to controlling transvascular fluid flux. A second major avenue of study centers around the role of the lymphatic system in the formation and alleviation of edema and the potential for pharmacological manipulation of the lymphatic system in a clinical setting. Studies have shown that numerous endogenous vasoactive agents, including catecholamines, acetylcholine, bradykinin, histamine, dopamine, serotonin, platelet activating factor, prostaglandin, neurokinin A and Endothelin-1 all stimulate lymphatic smooth muscle contraction. These experiments have been pivotal in helping to establish a sound database on the important role of lymphatic pumping in the function of the lymphatic system. Experiments addressing the alterations in microvascular permeability to macromolecule will continue to focus on the cellular and subcellular levels in an effort to determine the final common mediator of increased microvascular permeability. If a central common point in the cascade of events which result in increased permeability and edema formation can be identified, then this point would serve as a critical pharmacological target of the clinical treatment of various inflammatory diseases. The lymphatic contractility studies are being pursued to more clearly define the receptor mechanisms involved in the lymphatic smooth muscle activation by endogenous agents. It is hoped that his research will prove clinically beneficial in the many instances where increased transvascular fluid flux is a instigating or exacerbating circumstance of the disease process.