Walter A. Boyle, III, M.D.
Professor
Anesthesiology
Surgery
Associate Professor
Developmental Biology
Molecular Cell Biology Program
Neurosciences Program
|  |
Office Phone: 314-747-3581
Lab Phone: 314-362-8543
Other Phone:
FAX: 314-747-1710
Box: 8054
Lab Address: 5567 Clinical Sciences Research Building
Email: boylew@wustl.edu
Website: http://www.elysium.wustl.edu/wblab/
Keywords: calcium; vascular biology; inflammation; anesthetics; smooth muscle
Short Research Description: Molecular and cellular actions of anesthetics and septic stimuli on vascular tissue |
Research Abstract:
Studies in this laboratory are directed at understanding the molecular mechanisms involved in vascular smooth muscle contraction and relaxation. To this end, the lab has developed computer-based image analysis techniques to directly study microvessel reactivity under physiological conditions in vitro. Both pharmacological and biochemical tools have also been devised, including fluorescent techniques allowing real-time measurements of intracellular Ca2+ concentration ([Ca2+]i), electrophoresis and western blotting methods for separation and measurement of contractile protein isoforms, and membrane-permeabilization techniques for studying modulation of contractile protein function. The lab is specifically interested in the actions of volatile anesthetic agents which, as studies from this lab indicate, produce endothelium-independent vascular smooth muscle relaxation which is unrelated to changes in either ([Ca2+]i), or myosin phosphorylation. Ongoing studies are directed at elucidating the biochemical basis and physiological importance of this unique mechanism. Another active interest concerns the vascular effects of acute and chronic inflammation, particularly the microvascular changes that occur in septic shock. Utilizing genetically altered NOS2 (or iNOS) knock-out mice, recent studies from this lab indicate that induction of NOS2 gene expression in vascular smooth muscle plays a pivotal role in the development of catecholamine-resistant vasodilation following inflammatory or septic stimuli. Ongoing studies are directed at determining the effects of NOS2-derived nitric oxide on microvessel reactivity, endothelial function, and vascular permeability, and the mechanisms involved. |
Selected Publications:
Seegers H, Gross RW, Boyle W. Calcium-independent phospholipase A2-derived arachidonic acid is essential for endothelium-dependent relaxation by acetylcholine. J Pharmacol Exp Ther 2002 302:918-923.
Tsuneyoshi I, Yamada H, Kakihana Y, et al. Hemodynamic and metabolic effects of low-dose vasopression infusions in vasodilatory septic shock. Crit Care Med 2001 29:487-493.
Boyle WA, Parvathaneni LS, Bourlier V, et al. iNOS gene expression modulates microvascular responsiveness in endotoxin-challenged mice. Circ Res 2000 87:18-24.
Faury G, Li D, Keating MT, Mecham RP, Boyle WA. Relation between outer and luminal diameter in cannulated arteries. Am J Physiol 1999 277:H1745-1753.
Akata T, Boyle WA. Dual action of halothane on intracellular calcium stores of vascular smooth muscle. Anesthesiology 1996 84:580-595. |