This Article Full Text Full Text (PDF) All Versions of this Article: 39/7/2122    most recent STROKEAHA.107.508754v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Link, T. E. Articles by Wellman, G. C. PubMed PubMed Citation Articles by Link, T. E. Articles by Wellman, G. C. Related Collections Other Vascular biology Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage

(Stroke. 2008;39:2122.)
© 2008 American Heart Association, Inc.

Original Contributions

Oxyhemoglobin-Induced Expression of R-Type Ca²⁺ Channels in Cerebral Arteries

Timothy E. Link, MD; Kentaro Murakami, PhD; Micah Beem-Miller, BS; Bruce I. Tranmer, MD George C. Wellman, PhD

From the Department of Surgery, Division of Neurosurgery (T.E.L., B.I.T., G.C.W.) and the Department of Pharmacology (K.M., M.B.-M., G.C.W.), University of Vermont College of Medicine, Burlington.

Correspondence to Dr George C. Wellman, Department of Pharmacology, University of Vermont College of Medicine, 86 Beaumont Ave, Burlington, VT 05405. E-mail George.Wellman{at}uvm.edu

Background and Purpose— Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a major contributor to mortality and morbidity after aneurysm rupture. Recently, R-type voltage-dependent Ca²⁺ channel (VDCC) expression has been associated with increased cerebral artery constriction in a rabbit model of SAH. The goal of the present study was to examine whether the blood component oxyhemoglobin (oxyHb) can mimic the ability of SAH to cause R-type VDCC expression in the cerebral vasculature.

Methods— Rabbit cerebral arteries were organ cultured in serum-free media for up to 5 days in the presence or absence of purified oxyHb (10 µmol/L). Diameter changes in response to diltiazem, (L-type VDCC antagonist) and SNX-482 (R-type VDCC antagonist) were recorded at day 1, 3, or 5 in arteries constricted by elevated extracellular potassium. RT-PCR was performed on RNA extracted from arteries cultured for 5 days (±oxyHb) to assess VDCC expression.

Results— After 5 days, oxyHb-treated arteries were less sensitive and partially resistant to diltiazem compared to similar arteries organ cultured in the absence of oxyHb. Further, SNX-482 dilated arteries organ cultured for 5 days in the presence, but not in the absence, of oxyHb. RT-PCR revealed that oxyHb treated arteries expressed R-type VDCCs (Ca_V 2.3) in addition to L-type VDCCs (Ca_V 1.2), whereas untreated arteries expressed only Ca_V 1.2.

Conclusions— These results demonstrate that oxyhemoglobin exposure for 5 days induces the expression of Ca_V 2.3 in cerebral arteries. We propose that oxyhemoglobin contributes to enhanced cerebral artery constriction after SAH via the emergence of R-type VDCCs.

Key Words: calcium channels • cerebral arteries • subarachnoid hemorrhage • vasospasm • vascular smooth muscle