Studies in this laboratory are directed at understanding the molecular mechanism responsible for modulation of smooth muscle contraction. Intact resistance blood vessels are studied under physiologic conditions in vitro utilizing a computer-based image analysis system developed in this laboratory. Measurements of vessel diameter are made in real-time at video frame rates with simultaneous measurement of intracellular [Ca2+] ([Ca2+]i) using fluorescent probes. Membrane-permeabilized smooth muscle also is used to study contractile protein activation by Ca2+ and Ca2+ release from intracellular stores. A major interest in the laboratory is the mechanism whereby anesthetic gases produce smooth muscle relaxation in small blood vessels and airways. Work to date indicates that these agents induce smooth muscle relaxation by a unique mechanism in which contractile protein activation is inhibited, independent of changes in [Ca2+]i. Ongoing studies are directed at understanding the molecular mechanisms involved in this action.
Another major interest of this laboratory is the mechanism(s) involved in the endothelium-dependent smooth muscle relaxation and contractile oscillations. Current studies are directed at elucidating the role of phospholipase A2 products, particularly arachidonic acid and its metabolites, in these actions. Another project in the lab is directed at understanding the mechanism(s) involved in the decreased responsiveness of vascular smooth muscle from septic animals and humans. Current studies are directed at elucidating the role of increased expression of inducible nitric oxide synthase (iNOS) in this decreased responsiveness, utilizing both specific iNOS inhibitors and iNOS knockout animals.
Research Publications
Tsuneyoshi I, Zhang D, Boyle WA 3rd (2003 Sep). Ca2+- and myosin phosphorylation-independent relaxation by halothane in K+-depolarized rat mesenteric arteries. Anesthesiology. 99 (3): 656-65. Full Article >
Seegers HC, Gross RW, Boyle WA (2002 Sep). Calcium-independent phospholipase A(2)-derived arachidonic acid is essential for endothelium-dependent relaxation by acetylcholine. J Pharmacol Exp Ther. 302 (3): 918-23. Full Article >
Tsuneyoshi I, Boyle WA 3rd, Kanmura Y, Fujimoto T (2001). Hyperbaric hyperoxia suppresses growth of Staphylococcus aureus, including methicillin-resistant strains. J Anesth. 15 (1): 29-32. Full Article >
Boyle WA 3rd, Parvathaneni LS, Bourlier V, Sauter C, Laubach VE, Cobb JP (2000 Sep 29). iNOS gene expression modulates microvascular responsiveness in endotoxin-challenged mice. Circ Res. 87 (7): E18-24. Full Article >
Boyle WA 3rd, Parvathaneni LS, Bourlier V, Sauter C, Laubach VE, Cobb JP (2000 Sep 29). iNOS gene expression modulates microvascular responsiveness in endotoxin-challenged mice. Circ Res. 87 (7): E18-24. Full Article >
Faury G, Maher GM, Li DY, Keating MT, Mecham RP, Boyle WA (1999 Nov). Relation between outer and luminal diameter in cannulated arteries. Am J Physiol. 277 (5 Pt 2): H1745-53. Full Article >
Contact Info
Walter Boyle, M.D.
Office Location: 5567 Clinical Sciences Research Bldg.
Office Phone: 314-362-8543
Campus Box: 8054
Fax: 314- 747-1710
boylew@wustl.edu
http://elysium.wustl.edu/wblab/
