Robert M. Bryan, Jr., Ph.D.
Professor, Department of Anesthesiology, Vice-Chair for Basic Research
Ph.D., University of British Columbia
Postdoctoral, Duke University
Endothelium and Smooth Muscle Interactions
Our laboratory studies the control of cerebral circulation during normal and pathological states. Current projects involve the interaction between cerebrovascular endothelium and smooth muscle.
Project 1 seeks to understand the mechanism of dilation by endothelium-derived hyperpolarizing factor (EDHF) in cerebral arteries and arterioles. EDHF is an endothelial dependent mechanism, which does not involve nitric oxide or metabolites of arachidonic acid through the cyclooxygenase pathway. While the mechanism of EDHF dilations has not been fully elucidated, we do know that it involves calcium as a second messenger, potassium channels, and gap junctions.
Project 2 involves the regulation of cerebral blood flow following traumatic brain injury. After traumatic brain injury, EDHF is upregulated and may serve as a protective mechanism at a time when nitric oxide is diminished. Project 2 is seeking to determine the mechanism for the upregulation of EDHF.
Project 3 focuses on a new family of potassium channels, two-pore domain potassium channels, in cerebrovascular smooth muscle and endothelium. Potassium channels are important in the regulation of cerebral blood flow and members of this new family may function in concert with other channels for this purpose. Project 3 seeks to determine which members of the two-pore domain potassium channel family are present in cerebral vessels and how they function to regulate cerebral blood flow.
- Shafi NI, Andresen J, Marrelli SP and Bryan RM. Erythropoietin Potentiates EDHF-Mediated Dilations
in RatMiddle Cerebral Arteries. J Neurotrauma 25: 257-265, 2008.
- Bryan RM, Jr., Joseph BK, Lloyd E and Rusch NJ. Starring TREK-1: the next generation of vascular
K+ channels. Circ Res 101: 119-121, 2007.
- Rogers PA, Chilian WM, Bratz IN, Bryan RM Jr., Dick GM: H2O2 activates redox- and 4-aminopyridine-sensitive Kv channels in coronary vascular smooth muscle.Am.J.Physiol Heart and Circulatory Physiology 292:H1404-H1411, 2007.
- Marrelli SP, O'Neil RG, Brown RC, Bryan RM Jr.: PLA2 and TRPV4 channels regulate endothelial calcium in cerebral arteries.Am.J.Physiol Heart and Circulatory Physiology 292:H1390-H1397, 2007.
- Bryan RM Jr., You J, Phillips SC, Andresen JJ, Lloyd EE, Rogers PA, Dryer SE, Marrelli SP: Evidence for two-pore domain potassium channels in rat cerebral arteries. Am.J.Physiol Heart and Circulatory Physiology 291:H770-H780, 2006.
- Prisby RD, Wilkerson MK, Sokoya EM, Bryan RM Jr Wilson E, Delp MD: Endothelium-dependent vasodilation of cerebral arteries is altered with simulated microgravity through nitric oxide synthase and EDHF mechanisms. J.Appl.Physiol. 101:348-353 2006.
- Andresen JJ, Shafi NI, Bryan RM Jr: Effects of carbon monoxide and heme oxygenase inhibitors in cerebral vessels of rats and mice. AJP - Heart and Circulatory Physiology 291:H223-H230, 2006.
- Andresen J, Shafi NI, Bryan RM Jr: Endothelial influences on cerebrovascular tone. J.Appl.Physiol. 100:318-327 2006.
- Jiang X, Yang F, Tan H, Liao D, Bryan RM Jr, Randhawa JK, Rumbaut RE, Durante W, Schafer AI, Yang X, Wang H: Hyperhomocystinemia impairs endothelial function and eNOS activity via PKC activation.Arterioscler.Thromb.Vasc Biol. 25:2515-2521. 2005.
- You J, Golding EM, Bryan RM Jr: Arachidonic Acid Metabolites, Hydrogen Peroxide, and EDHF in Cerebral Arteries. Heart and Circulatory Physiology. 289(H1077):H1083. 2005.
- Yang J, Clark JW, Bryan RM Jr, Roberson CS: Mathematical Modeling of the Nitric Oxide/cGMP Pathway in the Vascular Smooth Muscle Cell. American Journal of Physiology. Heart and Circulatory Physiology. 289(2):H886-97. Aug 2005.
- Bryan RM Jr: Endothelium-derived Hyperpolarizing Factor: a Cousin to Nitric Oxide and Prostacyclin. Anesthesiology.102(1261):1277. Published. 2005.
- Wilkerson MK, Lesniewski LA, Golding EM, Bryan RM Jr, Amin A, Wilson E, Delp MD: Simulated Microgravity Enhances Cerebral Artery Vasoconstriction and Vascular REsistence Through Endothelial Nitric Oxide Mechanism. Heart and Circulatory Physiology. 288(4):H1652-61. Apr 2005.