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(Stroke. 2003;34:1473.)
© 2003 American Heart Association, Inc.

Original Contributions

Comparison of P₂ Receptor Subtypes Producing Dilation in Rat Intracerebral Arterioles

Tetsuyoshi Horiuchi, MD; Hans H. Dietrich, PhD; Kazuhiro Hongo, MD Ralph G. Dacey, Jr, MD

From the Department of Neurosurgery, Washington University School of Medicine, St Louis, Mo (T.H., H.H.D., R.G.D.), and Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto, Japan (T.H., K.H.).

Correspondence to Hans H. Dietrich, PhD, Department of Neurosurgery, Washington University School of Medicine, Box 8057, 660 S Euclid Ave, St Louis, MO 63110. E-mail DietrichH{at}Nsurg.wustl.edu

Background and Purpose— P₂ receptors are important regulators of cerebrovascular tone. However, there is functional heterogeneity of P_2Y receptors along the vascular tree, and the functionality of P_2Y receptors in small arterioles has not been studied in detail. We investigated the effects of activating P_2Y1 and P_2Y2 receptors and their underlying dilator mechanisms in rat intracerebral arterioles.

Methods— We used computer-aided videomicroscopy to measure diameter responses from isolated and pressurized rat penetrating arterioles (39.9±1.2 µm) to the natural P₂ receptor agonist ATP in addition to ADP-ß-S (P_2Y1-selective) and ATP--S (P_2Y2-selective) and inhibitors of signaling pathways.

Results— Extraluminal application of ATP--S and ADP-ß-S initiated a biphasic response (initial constriction followed by the secondary dilation) similar to ATP-induced responses. Pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (0.1 mmol/L; a P_2Y1 receptor antagonist) blocked ADP-ß-S- but not ATP--S-induced dilation and affected the ATP-mediated dilation at low concentrations. N-Monomethyl-L-arginine partially inhibited the dilation of ATP and ADP-ß-S but not ATP--S. High K⁺ saline suppressed the dilation of all agonists. Indomethacin had no effect.

Conclusions— Both P_2Y1 and P_2Y2 receptors are functionally present in cerebral arterioles. ATP stimulates P_2Y1 receptors at low concentrations, while high concentrations of ATP activate P_2Y2 in addition to P_2Y1 receptors. Nitric oxide is involved in P_2Y1 but not P_2Y2 receptor activation. Potassium channels play an important role in the regulation of P_2Y receptor-mediated dilation.

Key Words: adenosine • cerebral circulation • nitric oxide • potassium channels • receptors, purinergic P₂

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