The discovery of NO has led to the identification of multiple physiological roles for this gaseous second messenger in the microcirculation. We surmise that the local autocrine actions of NO that govern inflammation and vascular permeability in the microcirculation may be as important as its vasodilatory role in conduit vessels. Furthermore, the diverse function of NO may extend beyond the vascular bed. Recent findings using NOS inhibitors and eNOS (-/-) mice revealed an important role of endothelial derived nitric oxide in mediating lymphatic fluid flow in the microlym-phatic network (new reference #12). Therefore, future mechanistic studies and the development of novel reagents to faithfully manipulate the NO-sGC-PKG pathway will help dissect the physiological importance of NO in the microcirculation and microlymphatic beds.
Endothelium: The innermost layer of cells lining all blood vessels. Nitric oxide: A free radical gas produced by the enzyme nitric oxide synthase.
Permeability: The leakage of fluid or proteins from the circulation after tissue injury.
Vasodilation: Dilation of a blood vessel to increase blood flow.
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Dr. Sessa is a Professor in the Department of Pharmacology at Yale University and the Director of the Vascular Cell Signaling and Therapeutics Program. His laboratory research focuses on identifying cell biological and molecular pathway that influence the function of blood vessels during vessel remodeling, angiogenesis, and inflammation. His work is funded from the NIH.
Ms. Michelle I. Lin is a Ph.D. student examining how nitric oxide regulates vascular permeability.
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