Adenosine (ADO) is a potent cerebrovasodilator and has been proposed as a metabolic regulator of cerebral blood flow. However, the mechanism of action by which ADO causes vasodilation in the cerebral circulation is currently unknown. Furthermore, it is not known whether there is a heterogeneity in ADO vasoactivity or receptor subtype vascular tree of the cerebral circulation. This proposal outlines experiments designed to characterize the response of ADO specific to the location in the cerebral circulation and describe the mechanism of action of ADO. Thus, we wish to characterize and define the mechanism of action of ADO dilation in the cerebral circulation in a cell-specific manner, specifically with regard to receptor subtype activation and ion channel activation. Specifically we hypothesize that there is spatial heterogeneity within the cerebral circulation in the 1) vasoactive response to ADO and 2) specific ion channel activation by ADO receptor, and that 3) ADO acts at a specific ADO receptor subtype to cause vasodilation. The proposed experiments will employ techniques of both in vitro isolated perfused vessels and patch clamp studies of isolated vascular smooth muscle (VSM) myocytes as well as pharmacologic and molecular tools to identify specific ADO receptors.
The specific aims are to: 1) Characterize ADO vasoactivity in the arterial network in the rat cerebral circulation in a region-specific manner using an in vitro preparation; 2) Define the functional and molecular anatomy of ADO receptors and the cell-specific spatial distribution of the receptors in cerebrovascular vessels. 3) Define the role of KATP channels and KCa channels of ADO-induced vasodilation in the arterial network using an in vitro isolated perfused vessel with spontaneous tone and isolated single VSM cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
7K08NS043997-03
Application #
6840933
Study Section
Special Emphasis Panel (ZHL1-CSR-M (M1))
Program Officer
Jacobs, Tom P
Project Start
2002-04-03
Project End
2007-03-31
Budget Start
2003-12-01
Budget End
2004-03-31
Support Year
3
Fiscal Year
2003
Total Cost
$97,332
Indirect Cost
Name
Oregon Health and Science University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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West, G Alexander; Golshani, Kiarash J; Doyle, Kristian P et al. (2009) A new model of cortical stroke in the rhesus macaque. J Cereb Blood Flow Metab 29:1175-86
Iliff, Jeffrey J; Alkayed, Nabil J; Gloshani, Kiarash J et al. (2005) Cocaine- and amphetamine-regulated transcript (CART) peptide: a vasoactive role in the cerebral circulation. J Cereb Blood Flow Metab 25:1376-85