TRAINING IN PHARMACOLOGY, TOXICOLOGY & PHARMACEUTICAL SCIENCES 2008 ASPET SUMMER UNDERGRADUATE RESEARCH FELLOWSHIP OPPORTUNITY at the UNIVERSITY OF CINCINNATI
The Department of Pharmacology & Cell Biophysics, College of Medicine is pleased to offer this research project as part of the 2008 summer ASPET SURF Training Program offered  by the Department of Pharmacology & Cell Biophysics.  Students interested in this project are advised to contact Professor Rapoport to discover more about the project, learn what your responsibilities will be during the ten-week research training program.
2008 ASPET SURF Project #:  08 - 011 Faculty Supervisors/Mentors: Robert M. Rapoport, Ph.D. Associate Professor Seonghun Yoon, M.D. Pharmacology & Cell Biophysics, College of Medicine, University of Cincinnati Email:  rapoporm@uc.edu	Dr. Rapoport
Project Title: Role of Endothelin in Cerebral Vasoconstriction by Hypocarbia                        (Low Plasma CO2)
Research Program Description:  The research program of Drs. Rapoport and Yoon involves investigation of cerebral vasculature regulation by carbon dioxide in vivo using a rat model.  Lower levels of plasma carbon dioxide are recognized to be associated with constriction of the cerebral vasculature, while higher plasma carbon dioxide levels correlate with vasodilatation. Our specific research focus is on the former and, mechanistically, whether endothelin-1, mediates the vasoconstrictor response.  Endothelin-1, a potent vasoconstrictor, is released from a variety of cell types and the endothelium is a rich source of endothelin-1.  We propose that the elevated pH associated with lowered carbon dioxide causes release of endothelin-1 from the endothelium, which then constricts the cerebral vasculature.  To examine this possibility, we utilize an in situ preparation in which basilar artery diameter of the rat is observed and optically recorded following exposure to specific low levels of dissolved carbon dioxide in the plasma of the perfusate.  Responses in basilar artery diameter are then correlated with plasma CO2 before and after local administration of selective endothelin receptor antagonists.
ASPET SURF Research Project Description:  The ASPET SURF student will assist in set-up and surgical preparations of the model cerebral artery, and will learn to perform both in vitro and in vivo dose response studies in vascular pharmacology.  The identification and selection of receptor specific agonists and antagonists will permit the student to gain a practical appreciation of the relationships and mechanisms through which changes in physiological states translate to biological responses through receptor mediated molecular processes.  The expected results should permit the student to contribute significantly to an advance in understanding the “how” of why the cerebral blood vessels contract when exposed to decreasing partial pressures of dissolved plasma carbon dioxide, as might be experienced in hyperventilation, etc. Experimental design and scientific method will be emphasized as an active iterative process. The ASPET SURF student will be guided to read relevant scientific literature will interact with scientists at various levels (graduate students, postdoctoral fellows, junior faculty and faculty) and participate in the ASPET SURF Program seminars, etc. The SURF student will participate in scientific writing and will have the opportunity to earn authorship when the studies are published.